4bd3 | pdb_00004bd3

Phf19 links methylated lysine 36 of histone H3 to regulation of Polycomb activity

Structural highlights

4bd3 is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	M3L
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

PHF19_HUMAN Polycomb group (PcG) that specifically binds histone H3 trimethylated at 'Lys-36' (H3K36me3) and recruits the PRC2 complex. Probably involved in the transition from an active state to a repressed state in embryonic stem cells: acts by binding to H3K36me3, a mark for transcriptional activation, and recruiting H3K36me3 histone demethylases NO66 or KDM2B, leading to demethylation of H3K36 and recruitment of the PRC2 complex that mediates H3K27me3 methylation, followed by de novo silencing. Recruits the PRC2 complex to CpG islands and contributes to embryonic stem cell self-renewal. Also binds dimethylated at 'Lys-36' (H3K36me2). Isoform 1 and isoform 2 inhibit transcription from an HSV-tk promoter.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

Polycomb-group proteins are transcriptional repressors with essential roles in embryonic development. Polycomb repressive complex 2 (PRC2) contains the methyltransferase activity for Lys27. However, the role of other histone modifications in regulating PRC2 activity is just beginning to be understood. Here we show that direct recognition of methylated histone H3 Lys36 (H3K36me), a mark associated with activation, by the PRC2 subunit Phf19 is required for the full enzymatic activity of the PRC2 complex. Using NMR spectroscopy, we provide structural evidence for this interaction. Furthermore, we show that Phf19 binds to a subset of PRC2 targets in mouse embryonic stem cells and that this is required for their repression and for H3K27me3 deposition. These findings show that the interaction of Phf19 with H3K36me2 and H3K36me3 is essential for PRC2 complex activity and for proper regulation of gene repression in embryonic stem cells.

Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity.,Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2434. PMID:23104054^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wang S, Robertson GP, Zhu J. A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers. Gene. 2004 Dec 8;343(1):69-78. PMID:15563832 doi:https://dx.doi.org/10.1016/j.gene.2004.09.006
↑ Boulay G, Rosnoblet C, Guerardel C, Angrand PO, Leprince D. Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes. Biochem J. 2011 Mar 1;434(2):333-42. doi: 10.1042/BJ20100944. PMID:21143197 doi:https://dx.doi.org/10.1042/BJ20100944
↑ Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2434. PMID:23104054 doi:https://dx.doi.org/10.1038/nsmb.2434
↑ Brien GL, Gambero G, O'Connell DJ, Jerman E, Turner SA, Egan CM, Dunne EJ, Jurgens MC, Wynne K, Piao L, Lohan AJ, Ferguson N, Shi X, Sinha KM, Loftus BJ, Cagney G, Bracken AP. Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation. Nat Struct Mol Biol. 2012 Dec;19(12):1273-81. doi: 10.1038/nsmb.2449. Epub 2012, Nov 18. PMID:23160351 doi:https://dx.doi.org/10.1038/nsmb.2449
↑ Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2434. PMID:23104054 doi:https://dx.doi.org/10.1038/nsmb.2434

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OCA

[1] Wang S, Robertson GP, Zhu J. A novel human homologue of Drosophila polycomblike gene is up-regulated in multiple cancers. Gene. 2004 Dec 8;343(1):69-78. PMID:15563832 doi:https://dx.doi.org/10.1016/j.gene.2004.09.006

[2] Boulay G, Rosnoblet C, Guerardel C, Angrand PO, Leprince D. Functional characterization of human Polycomb-like 3 isoforms identifies them as components of distinct EZH2 protein complexes. Biochem J. 2011 Mar 1;434(2):333-42. doi: 10.1042/BJ20100944. PMID:21143197 doi:https://dx.doi.org/10.1042/BJ20100944

[3] Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2434. PMID:23104054 doi:https://dx.doi.org/10.1038/nsmb.2434

[4] Brien GL, Gambero G, O'Connell DJ, Jerman E, Turner SA, Egan CM, Dunne EJ, Jurgens MC, Wynne K, Piao L, Lohan AJ, Ferguson N, Shi X, Sinha KM, Loftus BJ, Cagney G, Bracken AP. Polycomb PHF19 binds H3K36me3 and recruits PRC2 and demethylase NO66 to embryonic stem cell genes during differentiation. Nat Struct Mol Biol. 2012 Dec;19(12):1273-81. doi: 10.1038/nsmb.2449. Epub 2012, Nov 18. PMID:23160351 doi:https://dx.doi.org/10.1038/nsmb.2449

[5] Ballare C, Lange M, Lapinaite A, Martin GM, Morey L, Pascual G, Liefke R, Simon B, Shi Y, Gozani O, Carlomagno T, Benitah SA, Di Croce L. Phf19 links methylated Lys36 of histone H3 to regulation of Polycomb activity. Nat Struct Mol Biol. 2012 Oct 28. doi: 10.1038/nsmb.2434. PMID:23104054 doi:https://dx.doi.org/10.1038/nsmb.2434

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4bd3 | pdb_00004bd3

Phf19 links methylated lysine 36 of histone H3 to regulation of Polycomb activity

Structural highlights

Function

Publication Abstract from PubMed

References

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