| Structural highlights
6ven is a 18 chain structure with sequence from [1], Atcc 18824, African clawed frog and Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| NonStd Res: | |
| Gene: | SET1, KMT2, YTX1, YHR119W (ATCC 18824), BRE2, CPS60, YLR015W (ATCC 18824), SDC1, CPS25, SAF19, YDR469W (ATCC 18824), SPP1, CPS40, SAF41, YPL138C (ATCC 18824), UBC (HUMAN), SWD3, CPS30, SAF35, YBR175W, YBR1237 (ATCC 18824), SWD1, CPS50, SAF49, YAR003W, FUN16 (ATCC 18824) |
| Activity: | [Histone_H3-lysine(4)_N-trimethyltransferase [Histone H3]-lysine(4) N-trimethyltransferase], with EC number 2.1.1.354 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[BRE2_YEAST] The COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation.[1] [2] [H2A1_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [UBC_HUMAN] Ubiquitin exists either covalently attached to another protein, or free (unanchored). When covalently bound, it is conjugated to target proteins via an isopeptide bond either as a monomer (monoubiquitin), a polymer linked via different Lys residues of the ubiquitin (polyubiquitin chains) or a linear polymer linked via the initiator Met of the ubiquitin (linear polyubiquitin chains). Polyubiquitin chains, when attached to a target protein, have different functions depending on the Lys residue of the ubiquitin that is linked: Lys-6-linked may be involved in DNA repair; Lys-11-linked is involved in ERAD (endoplasmic reticulum-associated degradation) and in cell-cycle regulation; Lys-29-linked is involved in lysosomal degradation; Lys-33-linked is involved in kinase modification; Lys-48-linked is involved in protein degradation via the proteasome; Lys-63-linked is involved in endocytosis, DNA-damage responses as well as in signaling processes leading to activation of the transcription factor NF-kappa-B. Linear polymer chains formed via attachment by the initiator Met lead to cell signaling. Ubiquitin is usually conjugated to Lys residues of target proteins, however, in rare cases, conjugation to Cys or Ser residues has been observed. When polyubiquitin is free (unanchored-polyubiquitin), it also has distinct roles, such as in activation of protein kinases, and in signaling.[3] [4] [SWD1_YEAST] The COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation.[5] [6] [SDC1_YEAST] The COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently activates gene expression by regulating transcription elongation and plays a role in telomere length maintenance.[7] [8] [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [SWD3_YEAST] The COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation.[9] [10] [H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [H2B11_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [SPP1_YEAST] The COMPASS (Set1C) complex specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation.[11] [12] [SET1_YEAST] Catalytic component of the COMPASS (Set1C) complex that specifically mono-, di- and trimethylates histone H3 to form H3K4me1/2/3, which subsequently plays a role in telomere length maintenance and transcription elongation regulation.[13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24]
Publication Abstract from PubMed
Methylation of histone H3K4 is a hallmark of actively transcribed genes that depends on mono-ubiquitination of histone H2B (H2B-Ub). H3K4 methylation in yeast is catalyzed by Set1, the methyltransferase subunit of COMPASS. We report here the cryo-EM structure of a six-protein core COMPASS subcomplex, which can methylate H3K4 and be stimulated by H2B-Ub, bound to a ubiquitinated nucleosome. Our structure shows that COMPASS spans the face of the nucleosome, recognizing ubiquitin on one face of the nucleosome and methylating H3 on the opposing face. As compared to the structure of the isolated core complex, Set1 undergoes multiple structural rearrangements to cement interactions with the nucleosome and with ubiquitin. The critical Set1 RxxxRR motif adopts a helix that mediates bridging contacts between the nucleosome, ubiquitin and COMPASS. The structure provides a framework for understanding mechanisms of trans-histone cross-talk and the dynamic role of H2B ubiquitination in stimulating histone methylation.
Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome.,Worden EJ, Zhang X, Wolberger C Elife. 2020 Jan 10;9. pii: 53199. doi: 10.7554/eLife.53199. PMID:31922488[25]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Huang F, Kirkpatrick D, Jiang X, Gygi S, Sorkin A. Differential regulation of EGF receptor internalization and degradation by multiubiquitination within the kinase domain. Mol Cell. 2006 Mar 17;21(6):737-48. PMID:16543144 doi:S1097-2765(06)00120-1
- ↑ Komander D. The emerging complexity of protein ubiquitination. Biochem Soc Trans. 2009 Oct;37(Pt 5):937-53. doi: 10.1042/BST0370937. PMID:19754430 doi:10.1042/BST0370937
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Roguev A, Schaft D, Shevchenko A, Pijnappel WW, Wilm M, Aasland R, Stewart AF. The Saccharomyces cerevisiae Set1 complex includes an Ash2 homologue and methylates histone 3 lysine 4. EMBO J. 2001 Dec 17;20(24):7137-48. PMID:11742990 doi:http://dx.doi.org/10.1093/emboj/20.24.7137
- ↑ Briggs SD, Bryk M, Strahl BD, Cheung WL, Davie JK, Dent SY, Winston F, Allis CD. Histone H3 lysine 4 methylation is mediated by Set1 and required for cell growth and rDNA silencing in Saccharomyces cerevisiae. Genes Dev. 2001 Dec 15;15(24):3286-95. doi: 10.1101/gad.940201. PMID:11751634 doi:http://dx.doi.org/10.1101/gad.940201
- ↑ Nagy PL, Griesenbeck J, Kornberg RD, Cleary ML. A trithorax-group complex purified from Saccharomyces cerevisiae is required for methylation of histone H3. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):90-4. Epub 2001 Dec 18. PMID:11752412 doi:http://dx.doi.org/10.1073/pnas.221596698
- ↑ Krogan NJ, Dover J, Khorrami S, Greenblatt JF, Schneider J, Johnston M, Shilatifard A. COMPASS, a histone H3 (Lysine 4) methyltransferase required for telomeric silencing of gene expression. J Biol Chem. 2002 Mar 29;277(13):10753-5. Epub 2002 Jan 22. PMID:11805083 doi:http://dx.doi.org/10.1074/jbc.C200023200
- ↑ Bryk M, Briggs SD, Strahl BD, Curcio MJ, Allis CD, Winston F. Evidence that Set1, a factor required for methylation of histone H3, regulates rDNA silencing in S. cerevisiae by a Sir2-independent mechanism. Curr Biol. 2002 Jan 22;12(2):165-70. PMID:11818070
- ↑ Bernstein BE, Humphrey EL, Erlich RL, Schneider R, Bouman P, Liu JS, Kouzarides T, Schreiber SL. Methylation of histone H3 Lys 4 in coding regions of active genes. Proc Natl Acad Sci U S A. 2002 Jun 25;99(13):8695-700. Epub 2002 Jun 11. PMID:12060701 doi:http://dx.doi.org/10.1073/pnas.082249499
- ↑ Santos-Rosa H, Schneider R, Bannister AJ, Sherriff J, Bernstein BE, Emre NC, Schreiber SL, Mellor J, Kouzarides T. Active genes are tri-methylated at K4 of histone H3. Nature. 2002 Sep 26;419(6905):407-11. Epub 2002 Sep 11. PMID:12353038 doi:http://dx.doi.org/10.1038/nature01080
- ↑ Boa S, Coert C, Patterton HG. Saccharomyces cerevisiae Set1p is a methyltransferase specific for lysine 4 of histone H3 and is required for efficient gene expression. Yeast. 2003 Jul 15;20(9):827-35. doi: 10.1002/yea.995. PMID:12845608 doi:http://dx.doi.org/10.1002/yea.995
- ↑ Santos-Rosa H, Schneider R, Bernstein BE, Karabetsou N, Morillon A, Weise C, Schreiber SL, Mellor J, Kouzarides T. Methylation of histone H3 K4 mediates association of the Isw1p ATPase with chromatin. Mol Cell. 2003 Nov;12(5):1325-32. doi: 10.1016/s1097-2765(03)00438-6. PMID:14636589 doi:http://dx.doi.org/10.1016/s1097-2765(03)00438-6
- ↑ Morillon A, Karabetsou N, Nair A, Mellor J. Dynamic lysine methylation on histone H3 defines the regulatory phase of gene transcription. Mol Cell. 2005 Jun 10;18(6):723-34. PMID:15949446 doi:http://dx.doi.org/S1097-2765(05)01315-8
- ↑ Nislow C, Ray E, Pillus L. SET1, a yeast member of the trithorax family, functions in transcriptional silencing and diverse cellular processes. Mol Biol Cell. 1997 Dec;8(12):2421-36. doi: 10.1091/mbc.8.12.2421. PMID:9398665 doi:http://dx.doi.org/10.1091/mbc.8.12.2421
- ↑ Corda Y, Schramke V, Longhese MP, Smokvina T, Paciotti V, Brevet V, Gilson E, Geli V. Interaction between Set1p and checkpoint protein Mec3p in DNA repair and telomere functions. Nat Genet. 1999 Feb;21(2):204-8. PMID:9988274 doi:http://dx.doi.org/10.1038/5991
- ↑ Worden EJ, Zhang X, Wolberger C. Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome. Elife. 2020 Jan 10;9. pii: 53199. doi: 10.7554/eLife.53199. PMID:31922488 doi:http://dx.doi.org/10.7554/eLife.53199
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