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Sequence-specific recruitment of transcriptional co-repressor Cabin1 by myocyte enhancer factor-2.

The myocyte enhancer factor-2 (MEF2) family of transcription factors has important roles in the development and function of T cells, neuronal cells and muscle cells. MEF2 is capable of repressing or activating transcription by association with a variety of co-repressors or co-activators in a calcium-dependent manner. Transcriptional repression by MEF2 has attracted particular attention because of its potential role in hypertrophic responses of cardiomyocytes. Several MEF2 co-repressors, such as Cabin1/Cain and class II histone deacetylases (HDACs), have been identified. However, the molecular mechanism of their recruitment to specific promoters by MEF2 remains largely unknown. Here we report a crystal structure of the MADS-box/MEF2S domain of human MEF2B bound to a motif of the transcriptional co-repressor Cabin1 and DNA at 2.2 A resolution. The crystal structure reveals a stably folded MEF2S domain on the surface of the MADS box. Cabin1 adopts an amphipathic alpha-helix to bind a hydrophobic groove on the MEF2S domain, forming a triple-helical interaction. Our studies of the ternary Cabin1/MEF2/DNA complex show a general mechanism by which MEF2 recruits transcriptional co-repressor Cabin1 and class II HDACs to specific DNA sites.

Pubmed ID: 12700764


  • Han A
  • Pan F
  • Stroud JC
  • Youn HD
  • Liu JO
  • Chen L



Publication Data

April 17, 2003

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Base Sequence
  • Binding Sites
  • Calcineurin
  • Crystallography, X-Ray
  • DNA
  • DNA-Binding Proteins
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • MADS Domain Proteins
  • MEF2 Transcription Factors
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Myogenic Regulatory Factors
  • Phosphoproteins
  • Protein Binding
  • Protein Structure, Tertiary
  • Repressor Proteins
  • Substrate Specificity
  • Transcription Factors
  • Transcription, Genetic