4r8p

Structural highlights

Function

[BMI1_HUMAN] Component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones; it mediates monoubiquitination of histone H2A 'Lys-119', rendering chromatin heritably changed in its expressibility. In the PRC1 complex, it is required to stimulate the E3 ubiquitin-protein ligase activity of RNF2/RING2.^{[1] [2] [3]} [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. [RING2_HUMAN] E3 ubiquitin-protein ligase that mediates monoubiquitination of 'Lys-119' of histone H2A, thereby playing a central role in histone code and gene regulation. H2A 'Lys-119' ubiquitination gives a specific tag for epigenetic transcriptional repression and participates in X chromosome inactivation of female mammals. May be involved in the initiation of both imprinted and random X inactivation. Essential component of a Polycomb group (PcG) multiprotein PRC1-like complex, a complex class required to maintain the transcriptionally repressive state of many genes, including Hox genes, throughout development. PcG PRC1 complex acts via chromatin remodeling and modification of histones, rendering chromatin heritably changed in its expressibility. E3 ubiquitin-protein ligase activity is enhanced by BMI1/PCGF4. Acts as the main E3 ubiquitin ligase on histone H2A of the PRC1 complex, while RING1 may rather act as a modulator of RNF2/RING2 activity.^{[4] [5] [6] [7] [8]} [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.

References

1. ↑ Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell. 2005 Dec 22;20(6):845-54. PMID:16359901 doi:10.1016/j.molcel.2005.12.002
2. ↑ Chagraoui J, Niessen SL, Lessard J, Girard S, Coulombe P, Sauvageau M, Meloche S, Sauvageau G. E4F1: a novel candidate factor for mediating BMI1 function in primitive hematopoietic cells. Genes Dev. 2006 Aug 1;20(15):2110-20. PMID:16882984 doi:http://dx.doi.org/20/15/2110
3. ↑ Li Z, Cao R, Wang M, Myers MP, Zhang Y, Xu RM. Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem. 2006 Jul 21;281(29):20643-9. Epub 2006 May 18. PMID:16714294 doi:10.1074/jbc.M602461200
4. ↑ Lee SJ, Choi JY, Sung YM, Park H, Rhim H, Kang S. E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme. FEBS Lett. 2001 Aug 10;503(1):61-4. PMID:11513855
5. ↑ Wang H, Wang L, Erdjument-Bromage H, Vidal M, Tempst P, Jones RS, Zhang Y. Role of histone H2A ubiquitination in Polycomb silencing. Nature. 2004 Oct 14;431(7010):873-8. Epub 2004 Sep 22. PMID:15386022 doi:10.1038/nature02985
6. ↑ Cao R, Tsukada Y, Zhang Y. Role of Bmi-1 and Ring1A in H2A ubiquitylation and Hox gene silencing. Mol Cell. 2005 Dec 22;20(6):845-54. PMID:16359901 doi:10.1016/j.molcel.2005.12.002
7. ↑ Li Z, Cao R, Wang M, Myers MP, Zhang Y, Xu RM. Structure of a Bmi-1-Ring1B polycomb group ubiquitin ligase complex. J Biol Chem. 2006 Jul 21;281(29):20643-9. Epub 2006 May 18. PMID:16714294 doi:10.1074/jbc.M602461200
8. ↑ Wang R, Taylor AB, Leal BZ, Chadwell LV, Ilangovan U, Robinson AK, Schirf V, Hart PJ, Lafer EM, Demeler B, Hinck AP, McEwen DG, Kim CA. Polycomb group targeting through different binding partners of RING1B C-terminal domain. Structure. 2010 Aug 11;18(8):966-75. PMID:20696397 doi:10.1016/j.str.2010.04.013
9. ↑ McGinty RK, Henrici RC, Tan S. Crystal structure of the PRC1 ubiquitylation module bound to the nucleosome. Nature. 2014 Oct 30;514(7524):591-6. doi: 10.1038/nature13890. PMID:25355358 doi:http://dx.doi.org/10.1038/nature13890