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

Aidong Han, Fan Pan, James C. Stroud, Hong Duk Youn, Jun O. Liu, Lin Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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 cells1-3. MEF2 is capable of repressing or activating transcription by association with a variety of co-repressors or co-activators in a calcium-dependent manner1,4,5. Transcriptional repression by MEF2 has attracted particular attention because of its potential role in hypertrophic responses of cardiomyocytes6. Several MEF2 co-repressors, such as Cabin1/Cain and class II histone deacetylases (HDACs), have been identified7-12. 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 Å resolution. The crystal structure reveals a stably folded MEF2S domain on the surface of the MADS box. Cabin1 adopts an amphipathic α-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.

Original languageEnglish (US)
Pages (from-to)730-734
Number of pages5
JournalNature
Volume422
Issue number6933
DOIs
StatePublished - Apr 17 2003

ASJC Scopus subject areas

  • General

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