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The chromatin-remodelling complex SNF2-related CBP activator protein (SRCAP) regulates chromatin structure in yeast by modulating the exchange of histone H2A for the H2A.Z variant. Here, we have investigated the contribution of H2A.Z-mediated chromatin remodelling to mammalian cell differentiation reprogramming. We show that the SRCAP subunit named ZNHIT1 or p18(Hamlet), which is a substrate of p38 MAPK, is recruited to the myogenin promoter at the onset of muscle differentiation, in a p38 MAPK-dependent manner. We also show that p18(Hamlet) is required for H2A.Z accumulation into this genomic region and for subsequent muscle gene transcriptional activation. Accordingly, downregulation of several subunits or the SRCAP complex impairs muscle gene expression. These results identify SRCAP/H2A.Z-mediated chromatin remodelling as a key early event in muscle differentiation-specific gene expression. We also propose a mechanism by which p38 MAPK-mediated signals are converted into chromatin structural changes, thereby facilitating transcriptional activation during mammalian cell differentiation.

Titel:	Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation.
Autor/in / Beteiligte Person:	Cuadrado, A ; Corrado, N ; Perdiguero, E ; Lafarga, V ; Muñoz-Canoves, P ; Nebreda, AR
Zeitschrift:	The EMBO journal, Jg. 29 (2010-06-16), Heft 12, S. 2014-25
Veröffentlichung:	2024- : [London] : Nature Publishing Group ; <i>Original Publication</i>: Eynsham, Oxford, England : Published for the European Molecular Biology Organization by IRL Press, [c1982-, 2010
Medientyp:	academicJournal
ISSN:	1460-2075 (electronic)
DOI:	10.1038/emboj.2010.85
Schlagwort:	Animals Cell Line DNA metabolism Mice Protein Binding Carrier Proteins metabolism Cell Differentiation Chromatin Assembly and Disassembly Histones metabolism Muscle Development Muscles physiology Trans-Activators metabolism
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [EMBO J] 2010 Jun 16; Vol. 29 (12), pp. 2014-25. <i>Date of Electronic Publication: </i>2010 May 14. MeSH Terms: Cell Differentiation* ; Chromatin Assembly and Disassembly* ; Muscle Development* ; Carrier Proteins / metabolism ; Histones / metabolism ; Muscles / physiology ; Trans-Activators / metabolism ; Animals ; Cell Line ; DNA / metabolism ; Mice ; Protein Binding References: Cell. 2007 Feb 23;128(4):693-705. (PMID: 17320507) ; Structure. 2008 Feb;16(2):166-79. (PMID: 18275809) ; Cell. 2000 Oct 27;103(3):411-22. (PMID: 11081628) ; EMBO J. 2007 Apr 18;26(8):2115-26. (PMID: 17380123) ; Mol Cell. 2008 Mar 14;29(5):611-24. (PMID: 18342607) ; Curr Biol. 2001 Aug 7;11(15):1183-7. (PMID: 11516949) ; Semin Cell Dev Biol. 2005 Aug-Oct;16(4-5):585-95. (PMID: 16099183) ; Genes Dev. 2007 Aug 1;21(15):1869-81. (PMID: 17671089) ; Mol Cell Biol. 2001 Sep;21(18):6270-9. (PMID: 11509669) ; Trends Cell Biol. 2006 Jan;16(1):36-44. (PMID: 16325404) ; Nat Genet. 2004 Jul;36(7):738-43. (PMID: 15208625) ; J Biol Chem. 2006 Jul 14;281(28):19369-77. (PMID: 16687393) ; Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1454-9. (PMID: 18218781) ; PLoS Biol. 2004 May;2(5):E131. (PMID: 15045029) ; Cell Cycle. 2007 Oct 1;6(19):2319-22. (PMID: 17700068) ; Curr Opin Genet Dev. 2005 Oct;15(5):528-35. (PMID: 16055324) ; PLoS Genet. 2006 Sep 29;2(9):e161. (PMID: 17009877) ; Genes Dev. 2009 Jul 1;23(13):1522-33. (PMID: 19515975) ; Nat Rev Genet. 2006 Jun;7(6):461-73. (PMID: 16708073) ; Nat Struct Mol Biol. 2007 Dec;14(12):1150-6. (PMID: 18026121) ; Mol Cell. 2003 Jul;12(1):51-62. (PMID: 12887892) ; Epigenetics. 2009 Nov 16;4(8):541-50. (PMID: 20009536) ; Nat Struct Biol. 2000 Dec;7(12):1121-4. (PMID: 11101893) ; Plant Physiol. 2007 Feb;143(2):893-901. (PMID: 17142478) ; Mol Cell Biol. 2003 Jan;23(1):370-81. (PMID: 12482988) ; Nat Struct Mol Biol. 2004 Jul;11(7):650-5. (PMID: 15195148) ; Cell. 2007 May 18;129(4):823-37. (PMID: 17512414) ; Mol Cell. 2003 Dec;12(6):1565-76. (PMID: 14690608) ; J Biol Chem. 2005 Apr 8;280(14):13665-70. (PMID: 15647280) ; J Biol Chem. 2007 Sep 7;282(36):26132-9. (PMID: 17617668) ; Nat Struct Mol Biol. 2005 Dec;12(12):1064-71. (PMID: 16299513) ; Cell. 2003 Mar 7;112(5):725-36. (PMID: 12628191) ; EMBO J. 2007 Mar 7;26(5):1245-56. (PMID: 17304211) ; Biochemistry. 2006 May 2;45(17):5671-7. (PMID: 16634648) ; Cell Stem Cell. 2009 Jan 9;4(1):80-93. (PMID: 19128795) ; Cell. 2005 Oct 21;123(2):233-48. (PMID: 16239142) ; Plant Cell. 2007 Jan;19(1):74-83. (PMID: 17220196) ; Cell Metab. 2008 Jan;7(1):33-44. (PMID: 18177723) Substance Nomenclature: 0 (Carrier Proteins) ; 0 (Histones) ; 0 (Trans-Activators) ; 0 (Znhit1 protein, mouse) ; 9007-49-2 (DNA) Entry Date(s): Date Created: 20100518 Date Completed: 20100629 Latest Revision: 20211020 Update Code: 20240513 PubMed Central ID: PMC2892367

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Essential role of p18Hamlet/SRCAP-mediated histone H2A.Z chromatin incorporation in muscle differentiation.