The histone variant macroh2a is an epigenetic regulator of key developmental genes

ABSTRACT The histone variants macroH2A1 and macroH2A2 are associated with X chromosome inactivation in female mammals. However, the physiological function of macroH2A proteins on autosomes

is poorly understood. Microarray-based analysis in human male pluripotent cells uncovered occupancy of both macroH2A variants at many genes encoding key regulators of development and cell

fate decisions. On these genes, the presence of macroH2A1+2 is a repressive mark that overlaps locally and functionally with Polycomb repressive complex 2. We demonstrate that macroH2A1+2

contribute to the fine-tuning of temporal activation of _HOXA_ cluster genes during neuronal differentiation. Furthermore, elimination of macroH2A2 function in zebrafish embryos produced

severe but specific phenotypes. Taken together, our data demonstrate that macroH2A variants constitute an important epigenetic mark involved in the concerted regulation of gene expression

programs during cellular differentiation and vertebrate development. Access through your institution Buy or subscribe This is a preview of subscription content, access via your institution

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about institutional subscriptions * Read our FAQs * Contact customer support SIMILAR CONTENT BEING VIEWED BY OTHERS POLYCOMB FUNCTION IN EARLY MOUSE DEVELOPMENT Article 12 July 2024

REGULATION, FUNCTIONS AND TRANSMISSION OF BIVALENT CHROMATIN DURING MAMMALIAN DEVELOPMENT Article 26 August 2022 SATB2 ACTS AS A GATEKEEPER FOR MAJOR DEVELOPMENTAL TRANSITIONS DURING EARLY

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Protoc._ 3, 59–69 (2008). Article  CAS  Google Scholar  Download references ACKNOWLEDGEMENTS We are indebted to T. Rasmussen, G. Dreyfuss (Howard Hughes Medical Institute) for the hnRNP U

4G5 antibody, S. Dimitrov and C. Pujades for reagents and members of the Di Croce laboratory for helpful discussions. This work was supported by grants from the Spanish “Ministerio de

Educación y Ciencia” and from “_La Marat_ó _TV3_” and Consolider. M.B. was supported by a Fellowship from Deutsche Forschungsgesellschaft (DFG) and I.U. by a predoctoral fellowship from

Spanish “Ministerio de Educación y Ciencia”. AUTHOR INFORMATION Author notes * Marcus Buschbeck & Lluís Morey Present address: Present addresses: Institute for Predictive and

Personalized Medicine of Cancer (IMPPC), Barcelona, Spain (M.B.); Centre for Epigenetics and BRIC, University of Copenhagen, Copenhagen, Denmark (L.M.)., AUTHORS AND AFFILIATIONS * Centre de

Regulació Genòmica (CRG), PRBB, Barcelona, Spain Marcus Buschbeck, Iris Uribesalgo, Indra Wibowo, Pau Rué, David Martin, Arantxa Gutierrez, Lluís Morey, Roderic Guigó, Hernán López-Schier 

& Luciano Di Croce * Departament de Física i Enginyeria Nuclear, Universitat Politècnica de Catalunya, Terrassa, Spain Pau Rué * Institució Catalana de Recerca i Estudis Avançats

(ICREA), Barcelona, Spain Luciano Di Croce Authors * Marcus Buschbeck View author publications You can also search for this author inPubMed Google Scholar * Iris Uribesalgo View author

publications You can also search for this author inPubMed Google Scholar * Indra Wibowo View author publications You can also search for this author inPubMed Google Scholar * Pau Rué View

author publications You can also search for this author inPubMed Google Scholar * David Martin View author publications You can also search for this author inPubMed Google Scholar * Arantxa

Gutierrez View author publications You can also search for this author inPubMed Google Scholar * Lluís Morey View author publications You can also search for this author inPubMed Google

Scholar * Roderic Guigó View author publications You can also search for this author inPubMed Google Scholar * Hernán López-Schier View author publications You can also search for this

author inPubMed Google Scholar * Luciano Di Croce View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS M.B., I.U., I.W., A.G. and L.M. performed

the experiments; M.B., P.R., D.M., R.G., H.L.-S. and L.D.C. analyzed the data; M.B. and L.D.C. designed the project and wrote the manuscript. CORRESPONDING AUTHOR Correspondence to Luciano

Di Croce. SUPPLEMENTARY INFORMATION SUPPLEMENTARY TEXT AND FIGURES Supplementary Figures 1–6 and Supplementary Tables 1–3 (PDF 4174 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT

THIS ARTICLE CITE THIS ARTICLE Buschbeck, M., Uribesalgo, I., Wibowo, I. _et al._ The histone variant macroH2A is an epigenetic regulator of key developmental genes. _Nat Struct Mol Biol_

16, 1074–1079 (2009). https://doi.org/10.1038/nsmb.1665 Download citation * Received: 06 February 2009 * Accepted: 07 August 2009 * Published: 06 September 2009 * Issue Date: October 2009 *

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