| Structural highlights
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
The Polycomb repressive complex 2 (PRC2) is a multicomponent histone H3K27 methyltransferase complex, best known for silencing the Hox genes during embryonic development. The Polycomb-like proteins PHF1, MTF2, and PHF19 are critical components of PRC2 by stimulating its catalytic activity in embryonic stem cells. The Tudor domains of PHF1/19 have been previously shown to be readers of H3K36me3 in vitro. However, some other studies suggest that PHF1 and PHF19 co-localize with the H3K27me3 mark but not H3K36me3 in cells. Here, we provide further evidence that PHF1 co-localizes with H3t in testis and its Tudor domain preferentially binds to H3tK27me3 over canonical H3K27me3 in vitro. Our complex structures of the Tudor domains of PHF1 and PHF19 with H3tK27me3 shed light on the molecular basis for preferential recognition of H3tK27me3 by PHF1 and PHF19 over canonical H3K27me3, implicating that H3tK27me3 might be a physiological ligand of PHF1/19.
Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19.,Dong C, Nakagawa R, Oyama K, Yamamoto Y, Zhang W, Dong A, Li Y, Yoshimura Y, Kamiya H, Nakayama JI, Ueda J, Min J Elife. 2020 Sep 1;9. pii: 58675. doi: 10.7554/eLife.58675. PMID:32869745[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:http://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:http://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:http://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:http://dx.doi.org/10.1038/nsmb.2449
- ↑ Dong C, Nakagawa R, Oyama K, Yamamoto Y, Zhang W, Dong A, Li Y, Yoshimura Y, Kamiya H, Nakayama JI, Ueda J, Min J. Structural basis for histone variant H3tK27me3 recognition by PHF1 and PHF19. Elife. 2020 Sep 1;9:e58675. PMID:32869745 doi:10.7554/eLife.58675
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