Jarid2 and PRC2, Partners in Regulating Gene Expression

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2010 Feb 4

PMID 20123894

Citations 282

Authors

Gang Li

Raphael Margueron

Manching Ku

Pierre Chambon

Bradley E Bernstein

Danny Reinberg

Affiliations

Soon will be listed here.

Abstract

The Polycomb group proteins foster gene repression profiles required for proper development and unimpaired adulthood, and comprise the components of the Polycomb-Repressive Complex 2 (PRC2) including the histone H3 Lys 27 (H3K27) methyltransferase Ezh2. How mammalian PRC2 accesses chromatin is unclear. We found that Jarid2 associates with PRC2 and stimulates its enzymatic activity in vitro. Jarid2 contains a Jumonji C domain, but is devoid of detectable histone demethylase activity. Instead, its artificial recruitment to a promoter in vivo resulted in corecruitment of PRC2 with resultant increased levels of di- and trimethylation of H3K27 (H3K27me2/3). Jarid2 colocalizes with Ezh2 and MTF2, a homolog of Drosophila Pcl, at endogenous genes in embryonic stem (ES) cells. Jarid2 can bind DNA and its recruitment in ES cells is interdependent with that of PRC2, as Jarid2 knockdown reduced PRC2 at its target promoters, and ES cells devoid of the PRC2 component EED are deficient in Jarid2 promoter access. In addition to the well-documented defects in embryonic viability upon down-regulation of Jarid2, ES cell differentiation is impaired, as is Oct4 silencing.

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References

Savla U, Benes J, Zhang J, Jones R . Recruitment of Drosophila Polycomb-group proteins by Polycomblike, a component of a novel protein complex in larvae. Development. 2008; 135(5):813-7. DOI: 10.1242/dev.016006. View

Kim T, Chen J, Sadoshima J, Lee Y . Jumonji represses atrial natriuretic factor gene expression by inhibiting transcriptional activities of cardiac transcription factors. Mol Cell Biol. 2004; 24(23):10151-60. PMC: 529025. DOI: 10.1128/MCB.24.23.10151-10160.2004. View

Schwartz Y, Kahn T, Nix D, Li X, Bourgon R, Biggin M . Genome-wide analysis of Polycomb targets in Drosophila melanogaster. Nat Genet. 2006; 38(6):700-5. DOI: 10.1038/ng1817. View

Cao R, Wang L, Wang H, Xia L, Erdjument-Bromage H, Tempst P . Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science. 2002; 298(5595):1039-43. DOI: 10.1126/science.1076997. View

Kuzmichev A, Jenuwein T, Tempst P, Reinberg D . Different EZH2-containing complexes target methylation of histone H1 or nucleosomal histone H3. Mol Cell. 2004; 14(2):183-93. DOI: 10.1016/s1097-2765(04)00185-6. View

Shirato H, Ogawa S, Nakajima K, Inagawa M, Kojima M, Tachibana M . A jumonji (Jarid2) protein complex represses cyclin D1 expression by methylation of histone H3-K9. J Biol Chem. 2008; 284(2):733-9. DOI: 10.1074/jbc.M804994200. View

Takeuchi T, Kojima M, Nakajima K, Kondo S . jumonji gene is essential for the neurulation and cardiac development of mouse embryos with a C3H/He background. Mech Dev. 1999; 86(1-2):29-38. DOI: 10.1016/s0925-4773(99)00100-8. View

Pasini D, Hansen K, Christensen J, Agger K, Cloos P, Helin K . Coordinated regulation of transcriptional repression by the RBP2 H3K4 demethylase and Polycomb-Repressive Complex 2. Genes Dev. 2008; 22(10):1345-55. PMC: 2377189. DOI: 10.1101/gad.470008. View

Zhao J, Sun B, Erwin J, Song J, Lee J . Polycomb proteins targeted by a short repeat RNA to the mouse X chromosome. Science. 2008; 322(5902):750-6. PMC: 2748911. DOI: 10.1126/science.1163045. View

10.

Squazzo S, OGeen H, Komashko V, Krig S, Jin V, Jang S . Suz12 binds to silenced regions of the genome in a cell-type-specific manner. Genome Res. 2006; 16(7):890-900. PMC: 1484456. DOI: 10.1101/gr.5306606. View

11.

Pasini D, Bracken A, Hansen J, Capillo M, Helin K . The polycomb group protein Suz12 is required for embryonic stem cell differentiation. Mol Cell Biol. 2007; 27(10):3769-79. PMC: 1899991. DOI: 10.1128/MCB.01432-06. View

12.

Sarma K, Margueron R, Ivanov A, Pirrotta V, Reinberg D . Ezh2 requires PHF1 to efficiently catalyze H3 lysine 27 trimethylation in vivo. Mol Cell Biol. 2008; 28(8):2718-31. PMC: 2293112. DOI: 10.1128/MCB.02017-07. View

13.

Jung J, Mysliwiec M, Lee Y . Roles of JUMONJI in mouse embryonic development. Dev Dyn. 2004; 232(1):21-32. DOI: 10.1002/dvdy.20204. View

14.

Kim H, Kang K, Kim J . AEBP2 as a potential targeting protein for Polycomb Repression Complex PRC2. Nucleic Acids Res. 2009; 37(9):2940-50. PMC: 2685092. DOI: 10.1093/nar/gkp149. View

15.

Cao R, Wang H, He J, Erdjument-Bromage H, Tempst P, Zhang Y . Role of hPHF1 in H3K27 methylation and Hox gene silencing. Mol Cell Biol. 2007; 28(5):1862-72. PMC: 2258785. DOI: 10.1128/MCB.01589-07. View

16.

Simon J, Kingston R . Mechanisms of polycomb gene silencing: knowns and unknowns. Nat Rev Mol Cell Biol. 2009; 10(10):697-708. DOI: 10.1038/nrm2763. View

17.

Patsialou A, Wilsker D, Moran E . DNA-binding properties of ARID family proteins. Nucleic Acids Res. 2005; 33(1):66-80. PMC: 546134. DOI: 10.1093/nar/gki145. View

18.

Klose R, Kallin E, Zhang Y . JmjC-domain-containing proteins and histone demethylation. Nat Rev Genet. 2006; 7(9):715-27. DOI: 10.1038/nrg1945. View

19.

Pandey R, Mondal T, Mohammad F, Enroth S, Redrup L, Komorowski J . Kcnq1ot1 antisense noncoding RNA mediates lineage-specific transcriptional silencing through chromatin-level regulation. Mol Cell. 2008; 32(2):232-46. DOI: 10.1016/j.molcel.2008.08.022. View

20.

Lee T, Jenner R, Boyer L, Guenther M, Levine S, Kumar R . Control of developmental regulators by Polycomb in human embryonic stem cells. Cell. 2006; 125(2):301-13. PMC: 3773330. DOI: 10.1016/j.cell.2006.02.043. View