Epigenetic Control of the Bone-master Runx2 Gene During Osteoblast-lineage Commitment by the Histone Demethylase JARID1B/KDM5B

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2015 Oct 11

PMID 26453309

Citations 46

Authors

Adriana Rojas

Rodrigo Aguilar

Berta Henriquez

Jane B Lian

Janet L Stein

Gary S Stein

Andre J van Wijnen

Brigitte van Zundert

Miguel L Allende

Martin Montecino

Affiliations

Soon will be listed here.

Abstract

Transcription factor Runx2 controls bone development and osteoblast differentiation by regulating expression of a significant number of bone-related target genes. Here, we report that transcriptional activation and repression of the Runx2 gene via its osteoblast-specific P1 promoter (encoding mRNA for the Runx2/p57 isoform) is accompanied by selective deposition and elimination of histone marks during differentiation of mesenchymal cells to the osteogenic and myoblastic lineages. These epigenetic profiles are mediated by key components of the Trithorax/COMPASS-like and Polycomb group complexes together with histone arginine methylases like PRMT5 and lysine demethylases like JARID1B/KDM5B. Importantly, knockdown of the H3K4me2/3 demethylase JARID1B, but not of the demethylases UTX and NO66, prevents repression of the Runx2 P1 promoter during myogenic differentiation of mesenchymal cells. The epigenetically forced expression of Runx2/p57 and osteocalcin, a classical bone-related target gene, under myoblastic-differentiation is accompanied by enrichment of the H3K4me3 and H3K27ac marks at the Runx2 P1 promoter region. Our results identify JARID1B as a key component of a potent epigenetic switch that controls mesenchymal cell fate into myogenic and osteogenic lineages.

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References

Ogryzko V, Schiltz R, Russanova V, Howard B, Nakatani Y . The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell. 1996; 87(5):953-9. DOI: 10.1016/s0092-8674(00)82001-2. View

Pal S, Vishwanath S, Erdjument-Bromage H, Tempst P, Sif S . Human SWI/SNF-associated PRMT5 methylates histone H3 arginine 8 and negatively regulates expression of ST7 and NM23 tumor suppressor genes. Mol Cell Biol. 2004; 24(21):9630-45. PMC: 522266. DOI: 10.1128/MCB.24.21.9630-9645.2004. View

Sinha K, Yasuda H, Coombes M, Dent S, de Crombrugghe B . Regulation of the osteoblast-specific transcription factor Osterix by NO66, a Jumonji family histone demethylase. EMBO J. 2009; 29(1):68-79. PMC: 2780536. DOI: 10.1038/emboj.2009.332. View

Zhao Q, Rank G, Tan Y, Li H, Moritz R, Simpson R . PRMT5-mediated methylation of histone H4R3 recruits DNMT3A, coupling histone and DNA methylation in gene silencing. Nat Struct Mol Biol. 2009; 16(3):304-311. PMC: 5120857. DOI: 10.1038/nsmb.1568. View

Gori F, Demay M . BIG-3, a novel WD-40 repeat protein, is expressed in the developing growth plate and accelerates chondrocyte differentiation in vitro. Endocrinology. 2003; 145(3):1050-4. DOI: 10.1210/en.2003-1314. View

Komori T, Yagi H, Nomura S, Yamaguchi A, Sasaki K, Deguchi K . Targeted disruption of Cbfa1 results in a complete lack of bone formation owing to maturational arrest of osteoblasts. Cell. 1997; 89(5):755-64. DOI: 10.1016/s0092-8674(00)80258-5. View

Lian J, Javed A, Zaidi S, Lengner C, Montecino M, van Wijnen A . Regulatory controls for osteoblast growth and differentiation: role of Runx/Cbfa/AML factors. Crit Rev Eukaryot Gene Expr. 2004; 14(1-2):1-41. View

Fabbrizio E, El Messaoudi S, Polanowska J, Paul C, Cook J, Lee J . Negative regulation of transcription by the type II arginine methyltransferase PRMT5. EMBO Rep. 2002; 3(7):641-5. PMC: 1084190. DOI: 10.1093/embo-reports/kvf136. View

Margueron R, Reinberg D . The Polycomb complex PRC2 and its mark in life. Nature. 2011; 469(7330):343-9. PMC: 3760771. DOI: 10.1038/nature09784. View

10.

Banck M, Li S, Nishio H, Wang C, Beutler A, Walsh M . The ZNF217 oncogene is a candidate organizer of repressive histone modifiers. Epigenetics. 2009; 4(2):100-6. PMC: 2929765. DOI: 10.4161/epi.4.2.7953. View

11.

Agger K, Cloos P, Christensen J, Pasini D, Rose S, Rappsilber J . UTX and JMJD3 are histone H3K27 demethylases involved in HOX gene regulation and development. Nature. 2007; 449(7163):731-4. DOI: 10.1038/nature06145. View

12.

Soutoglou E, Talianidis I . Coordination of PIC assembly and chromatin remodeling during differentiation-induced gene activation. Science. 2002; 295(5561):1901-4. DOI: 10.1126/science.1068356. View

13.

Lee H, Suh J, Kim A, Lee Y, Park S, Kim J . Histone deacetylase 1-mediated histone modification regulates osteoblast differentiation. Mol Endocrinol. 2006; 20(10):2432-43. DOI: 10.1210/me.2006-0061. View

14.

Hovhannisyan H, Zhang Y, Hassan M, Wu H, Glackin C, Lian J . Genomic occupancy of HLH, AP1 and Runx2 motifs within a nuclease sensitive site of the Runx2 gene. J Cell Physiol. 2012; 228(2):313-21. PMC: 3589976. DOI: 10.1002/jcp.22109. View

15.

Xiao Z, Hjelmeland A, Quarles L . Selective deficiency of the "bone-related" Runx2-II unexpectedly preserves osteoblast-mediated skeletogenesis. J Biol Chem. 2004; 279(19):20307-13. DOI: 10.1074/jbc.M401109200. View

16.

Hassan M, Tare R, Lee S, Mandeville M, Morasso M, Javed A . BMP2 commitment to the osteogenic lineage involves activation of Runx2 by DLX3 and a homeodomain transcriptional network. J Biol Chem. 2006; 281(52):40515-26. DOI: 10.1074/jbc.M604508200. View

17.

Stojic L, Jasencakova Z, Prezioso C, Stutzer A, Bodega B, Pasini D . Chromatin regulated interchange between polycomb repressive complex 2 (PRC2)-Ezh2 and PRC2-Ezh1 complexes controls myogenin activation in skeletal muscle cells. Epigenetics Chromatin. 2011; 4:16. PMC: 3180244. DOI: 10.1186/1756-8935-4-16. View

18.

Bernstein B, Mikkelsen T, Xie X, Kamal M, Huebert D, Cuff J . A bivalent chromatin structure marks key developmental genes in embryonic stem cells. Cell. 2006; 125(2):315-26. DOI: 10.1016/j.cell.2006.02.041. View

19.

Lee M, Javed A, Kim H, Shin H, Gutierrez S, Choi J . Transient upregulation of CBFA1 in response to bone morphogenetic protein-2 and transforming growth factor beta1 in C2C12 myogenic cells coincides with suppression of the myogenic phenotype but is not sufficient for osteoblast differentiation. J Cell Biochem. 1999; 73(1):114-25. View

20.

Cruzat F, Henriquez B, Villagra A, Hepp M, Lian J, van Wijnen A . SWI/SNF-independent nuclease hypersensitivity and an increased level of histone acetylation at the P1 promoter accompany active transcription of the bone master gene Runx2. Biochemistry. 2009; 48(30):7287-95. PMC: 2760825. DOI: 10.1021/bi9004792. View