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

  1. Martin Lange1,
  2. Bogac Kaynak1,8,
  3. Ulrike B. Forster2,
  4. Martje Tönjes1,
  5. Jenny J. Fischer1,
  6. Christina Grimm1,
  7. Jenny Schlesinger1,
  8. Steffen Just3,
  9. Ilona Dunkel1,
  10. Tammo Krueger1,
  11. Siegrun Mebus4,
  12. Hans Lehrach5,
  13. Rudi Lurz6,
  14. Johan Gobom7,
  15. Wolfgang Rottbauer3,
  16. Salim Abdelilah-Seyfried2, and
  17. Silke Sperling1,9
  1. 1 Group Cardiovascular Genetics, Department Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany;
  2. 2 Cell Polarity and Epithelial Development, Max Delbrück Center, Berlin 13125 Germany;
  3. 3 Molecular Cardiology, Ruprecht-Karls-Universität Heidelberg, Heidelberg 69120, Germany;
  4. 4 Department Pediatric Cardiology, German Heart Center Berlin, Berlin 13353, Germany;
  5. 5 Department Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany;
  6. 6 Microscopy Unit, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany;
  7. 7 Mass Spectrometry Group, Department Vertebrate Genomics, Max Planck Institute for Molecular Genetics, Berlin 14195, Germany

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.

Keywords

Footnotes

  • 8 Present address: Gladstone Institute of Cardiovascular Disease, San Francisco, CA 94158, USA.

  • 9 Corresponding author.

    9 E-Mail sperling{at}molgen.mpg.de; FAX 40-30-8413-1699.

  • Supplemental material is available at http://www.genesdev.org.

  • Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.471408.

    • Received January 16, 2008.
    • Accepted July 1, 2008.
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