2puy

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(New page: 200px<br /> <applet load="2puy" size="450" color="white" frame="true" align="right" spinBox="true" caption="2puy, resolution 1.43&Aring;" /> '''Crystal Structure o...)
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[[Image:2puy.jpg|left|200px]]<br /><applet load="2puy" size="350" color="white" frame="true" align="right" spinBox="true"
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<applet load="2puy" size="450" color="white" frame="true" align="right" spinBox="true"
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caption="2puy, resolution 1.43&Aring;" />
caption="2puy, resolution 1.43&Aring;" />
'''Crystal Structure of the BHC80 PHD finger'''<br />
'''Crystal Structure of the BHC80 PHD finger'''<br />
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==Overview==
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Histone methylation is crucial for regulating chromatin structure, gene, transcription and the epigenetic state of the cell. LSD1 is a, lysine-specific histone demethylase that represses transcription by, demethylating histone H3 on lysine 4 (ref. 1). The LSD1 complex contains a, number of proteins, all of which have been assigned roles in events, upstream of LSD1-mediated demethylation apart from BHC80 (also known as, PHF21A), a plant homeodomain (PHD) finger-containing protein. Here we, report that, in contrast to the PHD fingers of the bromodomain PHD finger, transcription factor (BPTF) and inhibitor of growth family 2 (ING2), which, bind methylated H3K4 (H3K4me3), the PHD finger of BHC80 binds unmethylated, H3K4 (H3K4me0), and this interaction is specifically abrogated by, methylation of H3K4. The crystal structure of the PHD finger of BHC80, bound to an unmodified H3 peptide has revealed the structural basis of the, recognition of H3K4me0. Knockdown of BHC80 by RNA inhibition results in, the de-repression of LSD1 target genes, and this repression is restored by, the reintroduction of wild-type BHC80 but not by a PHD-finger mutant that, cannot bind H3. Chromatin immunoprecipitation showed that BHC80 and LSD1, depend reciprocally on one another to associate with chromatin. These, findings couple the function of BHC80 to that of LSD1, and indicate that, unmodified H3K4 is part of the 'histone code'. They further raise the, possibility that the generation and recognition of the unmodified state on, histone tails in general might be just as crucial as post-translational, modifications of histone for chromatin and transcriptional regulation.
==About this Structure==
==About this Structure==
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2PUY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=2PUY OCA].
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2PUY is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2PUY OCA].
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==Reference==
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Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression., Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y, Nature. 2007 Aug 9;448(7154):718-22. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=17687328 17687328]
[[Category: Homo sapiens]]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Protein complex]]
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[[Category: transcription]]
[[Category: transcription]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 12 23:27:16 2007''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Wed Jan 23 12:05:06 2008''

Revision as of 10:05, 23 January 2008


2puy, resolution 1.43Å

Drag the structure with the mouse to rotate

Crystal Structure of the BHC80 PHD finger

Overview

Histone methylation is crucial for regulating chromatin structure, gene, transcription and the epigenetic state of the cell. LSD1 is a, lysine-specific histone demethylase that represses transcription by, demethylating histone H3 on lysine 4 (ref. 1). The LSD1 complex contains a, number of proteins, all of which have been assigned roles in events, upstream of LSD1-mediated demethylation apart from BHC80 (also known as, PHF21A), a plant homeodomain (PHD) finger-containing protein. Here we, report that, in contrast to the PHD fingers of the bromodomain PHD finger, transcription factor (BPTF) and inhibitor of growth family 2 (ING2), which, bind methylated H3K4 (H3K4me3), the PHD finger of BHC80 binds unmethylated, H3K4 (H3K4me0), and this interaction is specifically abrogated by, methylation of H3K4. The crystal structure of the PHD finger of BHC80, bound to an unmodified H3 peptide has revealed the structural basis of the, recognition of H3K4me0. Knockdown of BHC80 by RNA inhibition results in, the de-repression of LSD1 target genes, and this repression is restored by, the reintroduction of wild-type BHC80 but not by a PHD-finger mutant that, cannot bind H3. Chromatin immunoprecipitation showed that BHC80 and LSD1, depend reciprocally on one another to associate with chromatin. These, findings couple the function of BHC80 to that of LSD1, and indicate that, unmodified H3K4 is part of the 'histone code'. They further raise the, possibility that the generation and recognition of the unmodified state on, histone tails in general might be just as crucial as post-translational, modifications of histone for chromatin and transcriptional regulation.

About this Structure

2PUY is a Protein complex structure of sequences from Homo sapiens with as ligand. Full crystallographic information is available from OCA.

Reference

Recognition of unmethylated histone H3 lysine 4 links BHC80 to LSD1-mediated gene repression., Lan F, Collins RE, De Cegli R, Alpatov R, Horton JR, Shi X, Gozani O, Cheng X, Shi Y, Nature. 2007 Aug 9;448(7154):718-22. PMID:17687328

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