Regulation of muscle development by DPF3, a novel histone acetylation and methylation reader of the BAF chromatin remodeling complex

被引：169

作者：

Lange, Martin ^{[1
]}

Kaynak, Bogac ^{[1
]}

Forster, Ulrike B. ^{[2
]}

Toenjes, Martje ^{[1
]}

Fischer, Jenny J. ^{[1
]}

Grimm, Christina ^{[1
]}

Schlesinger, Jenny ^{[1
]}

Just, Steffen ^{[3
]}

Dunkel, Ilona ^{[1
]}

Krueger, Tammo ^{[1
]}

Mebus, Siegrun ^{[4
]}

Lehrach, Hans

Lurz, Rudi ^{[5
]}

Gobom, Johan ^{[6
]}

Rottbauer, Wolfgang ^{[3
]}

Abdelilah-Seyfried, Salim ^{[2
]}

Sperling, Silke ^{[1
]}

机构：

[1] Max Planck Inst Mol Genet, Grp Cardiovasc Genet, Dept Vertebrate Genom, D-14195 Berlin, Germany

[2] Max Delbruck Ctr, D-13125 Berlin, Germany

[3] Univ Heidelberg, D-69120 Heidelberg, Germany

[4] German Heart Ctr Berlin, Dept Pediat Cardiol, D-13353 Berlin, Germany

[5] Max Planck Inst Mol Genet, Microscopy Unit, D-14195 Berlin, Germany

[6] Max Planck Inst Mol Genet, Mass Spectrometry Grp, Dept Vertebrate Genom, D-14195 Berlin, Germany

来源：

GENES & DEVELOPMENT | 2008年 / 22卷 / 17期

关键词：

heart and skeletal muscle development and function; PHD finger; BAF chromatin remodeling complex; SMARCD3-BAF60; acetylated and methylated histones; Mef2;

D O I：

10.1101/gad.471408

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Chromatin remodeling and histone modifications facilitate access of transcription factors to DNA by promoting the unwinding and destabilization of histone-DNA interactions. We present DPF3, a new epigenetic key factor for heart and muscle development characterized by a double PHD finger. DPF3 is associated with the BAF chromatin remodeling complex and binds methylated and acetylated lysine residues of histone 3 and 4. Thus, DPF3 may represent the first plant homeodomains that bind acetylated lysines, a feature previously only shown for the bromodomain. During development Dpf3 is expressed in the heart and somites of mouse, chicken, and zebrafish. Morpholino knockdown of dpf3 in zebrafish leads to incomplete cardiac looping and severely reduced ventricular contractility, with disassembled muscular fibers caused by transcriptional deregulation of structural and regulatory proteins. Promoter analysis identified Dpf3 as a novel downstream target of Mef2a. Taken together, DPF3 adds a further layer of complexity to the BAF complex by representing a tissue-specific anchor between histone acetylations as well as methylations and chromatin remodeling. Furthermore, this shows that plant homeodomain proteins play a yet unexplored role in recruiting chromatin remodeling complexes to acetylated histones.

引用

页码：2370 / 2384

页数：15

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