Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

Modulation of chromatin position and gene expression by HDAC4 interaction with nucleoporins.

Class IIa histone deacetylases (HDACs) can modulate chromatin architecture and transcriptional activity, thereby participating in the regulation of cellular responses such as cardiomyocyte hypertrophy. However, the target genes of class IIa HDACs that control inducible cardiac growth and the broader mechanisms whereby these deacetylases modulate locus-specific gene expression within chromatin remain a mystery. Here, we used genome-wide promoter occupancy analysis, expression profiling, and primary cell validation to identify direct class IIa HDAC4 targets in cardiomyocytes. Simultaneously, we identified nucleoporin155 (Nup155) as an HDAC4-interacting protein. Mechanistically, we show that HDAC4 modulated the association of identified target genes with nucleoporins through interaction with Nup155. Moreover, a truncated mutant of Nup155 that cannot bind HDAC4 suppressed HDAC4-induced gene expression patterns and chromatin-nucleoporin association, suggesting that Nup155-mediated localization was required for HDAC4's effect on gene expression. We thus propose a novel mechanism of action for HDAC4, suggesting it can function to dynamically regulate gene expression through changes in chromatin-nucleoporin association.

Pubmed ID: 21464227


  • Kehat I
  • Accornero F
  • Aronow BJ
  • Molkentin JD


The Journal of cell biology

Publication Data

April 4, 2011

Associated Grants

  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Animals
  • Binding Sites
  • Cells, Cultured
  • Chromatin
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Histone Deacetylases
  • Humans
  • Nuclear Pore Complex Proteins
  • Rats
  • Rats, Sprague-Dawley
  • Repressor Proteins