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

DPF3 是 BAF 染色质重塑复合物的新型组蛋白乙酰化和甲基化读取器,它对肌肉发育的调节

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作者:Martin Lange, Bogac Kaynak, Ulrike B Forster, Martje Tönjes, Jenny J Fischer, Christina Grimm, Jenny Schlesinger, Steffen Just, Ilona Dunkel, Tammo Krueger, Siegrun Mebus, Hans Lehrach, Rudi Lurz, Johan Gobom, Wolfgang Rottbauer, Salim Abdelilah-Seyfried, Silke Sperling

Abstract

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.

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