Coregulator Codes of Transcriptional Regulation by Nuclear Receptors

These findings suggest that N-CoR associations with specific corepressor complexes are dynamically regulated and will exhibit promoter and cell-type specificity

Michael G. Rosenfeld; Christopher K. Glass

2002

Scholarcy highlights

  • Members of the nuclear receptor superfamily directly activate or repress target genes by binding to hormone response elements1 in promoter or enhancer regions, and by binding to other DNA sequence-specific activators and can inhibit the transcriptional activities of other classes of transcription factors by transrepression
  • Ligand-dependent recruitment of coactivators is dependent on activation function 2, which consists of a short conserved helical sequence within the C terminus of the ligand binding domain
  • Biochemical and expression cloning approaches have been used to identify a large number of factors that interact with nuclear receptors in either a ligand-independent or a ligand-dependent manner and are often components of large multiprotein complexes
  • As the number of potential coregulators clearly exceeds the capacity for direct interaction by a single receptor, the most plausible hypothesis is that transcriptional activation by nuclear receptors involves the actions of multiple factors
  • The yeast SWI1⁄7SNF complex facilitates the binding of sequence-specific transcription factors to nucleosomal DNA and can cause local changes in chromatin structure in an ATP-dependent manner
  • A specific conserved corepressor domain of N-CoR and SMRT has been shown to be capable of direct interaction with histone deacetylase 4 and 5. These findings suggest that N-CoR associations with specific corepressor complexes are dynamically regulated and will exhibit promoter and cell-type specificity
  • The potential for rapid exchange of nuclear receptors and cofactors has intriguing implications for the functional significance of ever expanding multiple receptors of coregulatory complexes

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