User:Madelyn Kasprzak/Sandbox 1 - Revision history

Madelyn Kasprzak: Added Specific Functions for the TET1-3 enzymes

2016-04-14T03:37:34Z

Added Specific Functions for the TET1-3 enzymes

←Older revision		Revision as of 03:37, 14 April 2016
Line 1:		Line 1:
-	==TET Enzymes==	+	=TET Enzymes=
	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

-	<StructureSection load='5cg9' size='~~400~~' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>	+	<StructureSection load='5cg9' size='320' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>

	== Structure ==		== Structure ==
Line 10:		Line 10:

	== Function ==		== Function ==
		+	===Common Function===
		+
	All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' />		All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' />

-	While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref>DOI 10.1038/nature12750</ref>	+	While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref name='Rahul M. Kohli & Yi Zhang'>DOI 10.1038/nature12750</ref>
		+
		+	===Specific Functions===
		+	Experimental data shows that the TET genes have different expression patterns and at different levels, which indicates that each of the TET enzymes do not fully overlap in their functionality.
		+
		+	TET1 is usually expressed in fetal heart, lung, and brain tissue and in adult skeletal muscle, thymus, and ovary. It is not generally expressed in adult heart, lung, and brain tissue. Moreover, studies have shown that TET1 expression in adult brain tissue is correlated with brain cancer. This occurs through TET1’s indirect activation of brain cancer-related genes such as EGFR, AKT3, CDK6, CCND2, and BRAF through creation of 5hmC which recruits the CHTOP-methylosome complex that activates these genes.<ref>DOI 10.1016/j.celrep.2014.08.071</ref>
		+
		+	TET2 is broadly expressed, but it is especially highly expressed in hematopoietic cells, which develop into blood cells. Regarding this, it is suggested that TET2 plays a role in hematopoiesis due to the presence of TET2 mutations in many myelodysplastic syndromes.<ref>DOI 10.1182/blood-2009-03-210039</ref><ref>DOI 10.1056/NEJMoa0810069</ref><ref>DOI 10.1038/ng.391</ref>
		+
		+	TET3 is highly expressed in zygotes and is involved with epigenetic chromatin reprogramming in the zygote after fertilization. Specifically, it plays a role in DNA demethylation of the paternal pronucleus before implantation.<ref name='Rahul M. Kohli & Yi Zhang' />

	== Disease ==		== Disease ==

-	== Relevance ==

	== Structural highlights ==		== Structural highlights ==

Madelyn Kasprzak: Move StructureSection tag back to enclosing Structure, Function, Disease, Relevance, and Structural highlights. Also made minor formatting edits.

2016-04-14T02:39:16Z

Move StructureSection tag back to enclosing Structure, Function, Disease, Relevance, and Structural highlights. Also made minor formatting edits.

←Older revision		Revision as of 02:39, 14 April 2016
Line 3:		Line 3:

	<StructureSection load='5cg9' size='400' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>		<StructureSection load='5cg9' size='400' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>
-	</StructureSection>

	== Structure ==		== Structure ==
-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases.
		+
		+	In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />

	== Function ==		== Function ==
-	All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref>DOI 10.1038/nature12750</ref>	+	All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' />
		+
		+	While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref>DOI 10.1038/nature12750</ref>

	== Disease ==		== Disease ==
Line 16:		Line 19:

	== Structural highlights ==		== Structural highlights ==
		+
		+	</StructureSection>

	== References ==		== References ==
	<references/>		<references/>

Madelyn Kasprzak: Moved the StructureSection tag to not enclose anything and made it larger to 400px

2016-04-14T02:27:54Z

Moved the StructureSection tag to not enclose anything and made it larger to 400px

←Older revision		Revision as of 02:27, 14 April 2016
Line 2:		Line 2:
	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

-	<StructureSection load='5cg9' size='~~300~~' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>	+	<StructureSection load='5cg9' size='400' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>
		+	</StructureSection>

	== Structure ==		== Structure ==
	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
-
-	</StructureSection>

	== Function ==		== Function ==

Madelyn Kasprzak: Tried moving the StructureSection tag to enclose only the Structure section

2016-04-14T02:25:58Z

Tried moving the StructureSection tag to enclose only the Structure section

←Older revision		Revision as of 02:25, 14 April 2016
Line 1:		Line 1:
	==TET Enzymes==		==TET Enzymes==
-	<StructureSection load='5cg9' size='300' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>
-
	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>
		+
		+	<StructureSection load='5cg9' size='300' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>

	== Structure ==		== Structure ==
	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
		+
		+	</StructureSection>

	== Function ==		== Function ==
Line 16:		Line 18:
	== Structural highlights ==		== Structural highlights ==

-	</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

Madelyn Kasprzak: Added General Function information

2016-04-14T02:22:32Z

Added General Function information

←Older revision		Revision as of 02:22, 14 April 2016
Line 6:		Line 6:
	== Structure ==		== Structure ==
	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />		The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />
-

	== Function ==		== Function ==
-		+	All three TET enzymes and their isoforms are involved in the biochemical pathway that converts 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). They also regulate the further conversions of 5hmC to 5-formylcytosine (5fC) and then 5fC to 5-carboxylcytosine (5caC).<ref name='He et al.'>DOI: 10.1126/science.1210944</ref> Although experimental data shows that TET3 does so to a lesser extent than TET1 and TET2.<ref name='He et al.' /> While the oxidation performed by TET enzymes was originally thought to be a source of DNA damage, new research has implied that this catalytic activity may actually be the initial steps of a process of DNA demethylation. This hypothesized DNA demethylation pathway starts with the conversion of 5mC to 5caC after several rounds of oxidation by TET enzymes. The next step is the removal of the modified cytosine base by thymine DNA glycosylase (TDG) which leaves an abasic site on the DNA. The last step is then the process of base excision repair in which a new unmodified cytosine is regenerated at the site, thus completing the process of DNA demethylation.<ref name='He et al.' /><ref>DOI 10.1038/nature12750</ref>

	== Disease ==		== Disease ==
Line 16:		Line 15:

	== Structural highlights ==		== Structural highlights ==
-
-	This is a sample scene created with SAT to <scene name="/12/3456/Sample/1">color</scene> by Group, and another to make <scene name="/12/3456/Sample/2">a transparent representation</scene> of the protein. You can make your own scenes on SAT starting from scratch or loading and editing one of these sample scenes.

	</StructureSection>		</StructureSection>
	== References ==		== References ==
	<references/>		<references/>

Madelyn Kasprzak: Added some additional notes to the end of the structure section and Fixed the double reference listing error

2016-04-14T00:58:04Z

Added some additional notes to the end of the structure section and Fixed the double reference listing error

←Older revision		Revision as of 00:58, 14 April 2016
Line 5:		Line 5:

	== Structure ==		== Structure ==
-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref~~>DOI 10~~.~~1007~~/~~978-1-4419-9967-2_3</ref~~> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref>DOI 10.1371/journal.pone.0016627</ref>	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref name='Kinney et al.'>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref name='Kinney et al.' /> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref name='Frauer et al.'>DOI 10.1371/journal.pone.0016627</ref> Frauer et al. also speculated that the CXXC domain of TET1 may be involved with protein-protein interactions instead of DNA binding.<ref name='Frauer et al.' />

Madelyn Kasprzak at 00:44, 14 April 2016

2016-04-14T00:44:38Z

←Older revision		Revision as of 00:44, 14 April 2016
Line 5:		Line 5:

	== Structure ==		== Structure ==
-	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site. This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. ~~The~~ TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). ~~Evidence suggests~~ that the KFGG motif increases affinity for unmethylated DNA ~~[1]~~. While TET1 still prefers unmethylated CpGs in DNA over methylated CpGs with an approximate ratio of 3 : 1, this is much less than DNMT1’s ratio of 48 to 1 in its preference for unmethylated CpGs over methylated CpGs [2]. ~~This agrees with the fact that DNMTs methylate DNA whereas TET enzymes are suspected to be agents in active DNA demethylation, specifically cytosine~~.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site.<ref>DOI 10.1007/978-1-4419-9967-2_3</ref> This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. However, the TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). A study conducted by Frauer et al. in 2011 showed that the isolated CXXC domain of TET1 has no DNA binding activity, which agrees with the evidence suggesting that the KFGG motif increases affinity for unmethylated DNA.<ref>DOI 10.1371/journal.pone.0016627</ref>


	== Function ==		== Function ==
		+
		+
	== Disease ==		== Disease ==

Madelyn Kasprzak at 00:21, 14 April 2016

2016-04-14T00:21:21Z

←Older revision		Revision as of 00:21, 14 April 2016
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	== Structure ==		== Structure ==
-	The TET enzymes have a cysteine-rich ~~domain~~ followed by a double stranded beta-helix (DSBH) ~~region~~ near their C-terminus. In addition, TET1 ~~and TET3 both have~~ a CXXC-type zinc finger domain near ~~their~~ N-terminus. The TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). Evidence suggests that the KFGG motif increases affinity for unmethylated DNA [1]. While TET1 still prefers unmethylated CpGs in DNA over methylated CpGs with an approximate ratio of 3 : 1, this is much less than DNMT1’s ratio of 48 to 1 in its preference for unmethylated CpGs over methylated CpGs [2]. This agrees with the fact that DNMTs methylate DNA whereas TET enzymes are suspected to be agents in active DNA demethylation, specifically cytosine.	+	The TET enzymes have a cysteine-rich region closely followed by a double stranded beta-helix (DSBH) domain near their C-terminus.<ref>DOI 10.1007/978-1-4419-9967-2_3</ref> The DSBH domain contains three Fe<sup>2+</sup> binding sites and an α-ketoglutarate binding site. This DSBH domain, along with the preceding cysteine-rich region, performs the main catalytic activity of these enzymes and more generally, for all α-ketoglutarate oxygenases. In addition, TET1 has a CXXC-type zinc finger domain near the N-terminus. The TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). Evidence suggests that the KFGG motif increases affinity for unmethylated DNA [1]. While TET1 still prefers unmethylated CpGs in DNA over methylated CpGs with an approximate ratio of 3 : 1, this is much less than DNMT1’s ratio of 48 to 1 in its preference for unmethylated CpGs over methylated CpGs [2]. This agrees with the fact that DNMTs methylate DNA whereas TET enzymes are suspected to be agents in active DNA demethylation, specifically cytosine.

Madelyn Kasprzak at 23:47, 13 April 2016

2016-04-13T23:47:37Z

←Older revision		Revision as of 23:47, 13 April 2016
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	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>		TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

-	== Structure ~~and Function~~ ==	+	== Structure ==
		+	The TET enzymes have a cysteine-rich domain followed by a double stranded beta-helix (DSBH) region near their C-terminus. In addition, TET1 and TET3 both have a CXXC-type zinc finger domain near their N-terminus. The TET1 CXXC domain lacks the conserved lysine-phenylalanine-glycine-glycine (KFGG) motif commonly seen within the CXXC domains of other DNA binding proteins, such as DNA methyltransferase-1 (DNMT1). Evidence suggests that the KFGG motif increases affinity for unmethylated DNA [1]. While TET1 still prefers unmethylated CpGs in DNA over methylated CpGs with an approximate ratio of 3 : 1, this is much less than DNMT1’s ratio of 48 to 1 in its preference for unmethylated CpGs over methylated CpGs [2]. This agrees with the fact that DNMTs methylate DNA whereas TET enzymes are suspected to be agents in active DNA demethylation, specifically cytosine.

		+
		+	== Function ==
	== Disease ==		== Disease ==

Madelyn Kasprzak: Added an introduction for the TET enzymes

2016-04-13T23:10:12Z

Added an introduction for the TET enzymes

←Older revision		Revision as of 23:10, 13 April 2016
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	==TET Enzymes==		==TET Enzymes==
-	<StructureSection load='~~1stp~~' size='~~340~~' side='right' caption='~~Caption for this structure~~' scene=''>	+	<StructureSection load='5cg9' size='300' side='right' caption='TET-like protein in Naegleria gruberi in complex with DNA containing 5hmC.' scene=''>
-	~~This is~~ a ~~default text for your page '''Madelyn Kasprzak/Sandbox~~ 1~~'''~~. ~~Click above on~~ '''~~edit this page~~'~~'' to modify. Be careful with~~ the ~~< and > signs~~.	+
-	~~You may include any references to papers as in: the use of JSmol in Proteopedia~~ <ref>DOI 10.~~1002~~/~~ijch~~.~~201300024~~</ref> ~~or to the article describing Jmol <ref>PMID:21638687</ref> to the rescue.~~	+	TET enzymes are a family of [[Dioxygenase\|dioxygenases]] that are involved in the process of oxidizing methylated cytosine. Members of this family include ten-eleven translocation methylcytosine dioxygenase 1 (TET1), methylcytosine dioxygenase TET2, and methylcytosine dioxygenase TET3. The gene for the first of these proteins, TET1, was identified when it was determined to be fused to the ''Mixed Lineage Leukemia'' (MLL) gene as a result of a translocation event that occurred between chromosomes ten and eleven (hence the name). <ref>DOI 10.1038/sj.leu.2402834</ref>

	== Structure and Function ==		== Structure and Function ==