Tet-Mediated DNA Demethylation Is Required for SWI/SNF-Dependent Chromatin Remodeling and Histone-Modifying Activities That Trigger Expression of the Sp7 Osteoblast Master Gene During Mesenchymal Lineage Commitment

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 2017 Aug 9

PMID 28784721

Citations 18

Authors

Hugo Sepulveda

Alejandro Villagra

Martin Montecino

Affiliations

Soon will be listed here.

Abstract

Here we assess histone modification, chromatin remodeling, and DNA methylation processes that coordinately control the expression of the bone master transcription factor Sp7 (osterix) during mesenchymal lineage commitment in mammalian cells. We find that Sp7 gene silencing is mediated by DNA methyltransferase1/3 (DNMT1/3)-, histone deacetylase 1/2/4 (HDAC1/2/4)-, Setdb1/Suv39h1-, and Ezh1/2-containing complexes. In contrast, Sp7 gene activation involves changes in histone modifications, accompanied by decreased nucleosome enrichment and DNA demethylation mediated by SWI/SNF- and Tet1/Tet2-containing complexes, respectively. Inhibition of DNA methylation triggers changes in the histone modification profile and chromatin-remodeling events leading to Sp7 gene expression. Tet1/Tet2 silencing prevents Sp7 expression during osteoblast differentiation as it impairs DNA demethylation and alters the recruitment of histone methylase (COMPASS)-, histone demethylase (Jmjd2a/Jmjd3)-, and SWI/SNF-containing complexes to the Sp7 promoter. The dissection of these interconnected epigenetic mechanisms that govern Sp7 gene activation reveals a hierarchical process where regulatory components mediating DNA demethylation play a leading role.

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References

Kruidenier L, Chung C, Cheng Z, Liddle J, Che K, Joberty G . A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Nature. 2012; 488(7411):404-8. PMC: 4691848. DOI: 10.1038/nature11262. View

Helin K, Dhanak D . Chromatin proteins and modifications as drug targets. Nature. 2013; 502(7472):480-8. DOI: 10.1038/nature12751. View

Barbuto R, Mitchell J . Regulation of the osterix (Osx, Sp7) promoter by osterix and its inhibition by parathyroid hormone. J Mol Endocrinol. 2013; 51(1):99-108. PMC: 3685218. DOI: 10.1530/JME-12-0251. View

Shechter D, Dormann H, Allis C, Hake S . Extraction, purification and analysis of histones. Nat Protoc. 2007; 2(6):1445-57. DOI: 10.1038/nprot.2007.202. View

Lee J, Lee T . Effects of histone acetylation and CpG methylation on the structure of nucleosomes. Biochim Biophys Acta. 2012; 1824(8):974-82. PMC: 3565240. DOI: 10.1016/j.bbapap.2012.05.006. View

Jones P, Taylor S . Cellular differentiation, cytidine analogs and DNA methylation. Cell. 1980; 20(1):85-93. DOI: 10.1016/0092-8674(80)90237-8. View

Long F . Building strong bones: molecular regulation of the osteoblast lineage. Nat Rev Mol Cell Biol. 2011; 13(1):27-38. DOI: 10.1038/nrm3254. View

Zhang C, Cho K, Huang Y, Lyons J, Zhou X, Sinha K . Inhibition of Wnt signaling by the osteoblast-specific transcription factor Osterix. Proc Natl Acad Sci U S A. 2008; 105(19):6936-41. PMC: 2383965. DOI: 10.1073/pnas.0710831105. View

Hashimoto H, Vertino P, Cheng X . Molecular coupling of DNA methylation and histone methylation. Epigenomics. 2011; 2(5):657-69. PMC: 3039846. DOI: 10.2217/epi.10.44. View

10.

Williams K, Christensen J, Pedersen M, Johansen J, Cloos P, Rappsilber J . TET1 and hydroxymethylcytosine in transcription and DNA methylation fidelity. Nature. 2011; 473(7347):343-8. PMC: 3408592. DOI: 10.1038/nature10066. View

11.

Lee J, Lee Y, Kim M, Choi J, Park E, Kim S . Methylation of the mouse DIx5 and Osx gene promoters regulates cell type-specific gene expression. Mol Cells. 2006; 22(2):182-8. View

12.

Zhang T, Termanis A, Ozkan B, Bao X, Culley J, de Lima Alves F . G9a/GLP Complex Maintains Imprinted DNA Methylation in Embryonic Stem Cells. Cell Rep. 2016; 15(1):77-85. PMC: 4826439. DOI: 10.1016/j.celrep.2016.03.007. View

13.

Cano-Rodriguez D, Gjaltema R, Jilderda L, Jellema P, Dokter-Fokkens J, Ruiters M . Writing of H3K4Me3 overcomes epigenetic silencing in a sustained but context-dependent manner. Nat Commun. 2016; 7:12284. PMC: 4987519. DOI: 10.1038/ncomms12284. View

14.

He Y, Li B, Li Z, Liu P, Wang Y, Tang Q . Tet-mediated formation of 5-carboxylcytosine and its excision by TDG in mammalian DNA. Science. 2011; 333(6047):1303-7. PMC: 3462231. DOI: 10.1126/science.1210944. View

15.

Zhou X, Zhang Z, Feng J, Dusevich V, Sinha K, Zhang H . Multiple functions of Osterix are required for bone growth and homeostasis in postnatal mice. Proc Natl Acad Sci U S A. 2010; 107(29):12919-24. PMC: 2919908. DOI: 10.1073/pnas.0912855107. View

16.

Valinluck V, Sowers L . Endogenous cytosine damage products alter the site selectivity of human DNA maintenance methyltransferase DNMT1. Cancer Res. 2007; 67(3):946-50. DOI: 10.1158/0008-5472.CAN-06-3123. View

17.

Woan K, Sahakian E, Sotomayor E, Seto E, Villagra A . Modulation of antigen-presenting cells by HDAC inhibitors: implications in autoimmunity and cancer. Immunol Cell Biol. 2011; 90(1):55-65. PMC: 3990411. DOI: 10.1038/icb.2011.96. View

18.

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

19.

Laurent L, Wong E, Li G, Huynh T, Tsirigos A, Ong C . Dynamic changes in the human methylome during differentiation. Genome Res. 2010; 20(3):320-31. PMC: 2840979. DOI: 10.1101/gr.101907.109. View

20.

Wang P, Lin C, Smith E, Guo H, Sanderson B, Wu M . Global analysis of H3K4 methylation defines MLL family member targets and points to a role for MLL1-mediated H3K4 methylation in the regulation of transcriptional initiation by RNA polymerase II. Mol Cell Biol. 2009; 29(22):6074-85. PMC: 2772563. DOI: 10.1128/MCB.00924-09. View