α-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by antagonizing histone deacetylase 7

Sharmistha Chakraborty, Erin L. Reineke, Minh Lam, Xiaofang Li, Yu Liu, Chengzhuo Gao, Simran Khurana, Hung Ying Kao

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

Histone deacetylase 7 (HDAC7) is a member of class IIa HDACs that regulate myocyte enhancer factor-2 (MEF2)-mediated transcription and participate in multiple cellular processes such as T cell apoptosis. We have identified α-actinin 1 and 4 as class IIa HDAC-interacting proteins. The interaction domains are mapped to C terminus of α-actinin 4 and amino acids 72-172 of HDAC7. A point mutation in HDAC7 that disrupts its association with MEF2A also disrupts its association with α-actinin 4, indicating that MEF2A and α-actinin 4 binding sites largely overlap. We have also isolated a novel splice variant of α-actinin 4 that is predominantly localized in the nucleus, a pattern distinct from the full-length α-actinin 4, which is primarily distributed in the cytoplasm and plasma membrane. Using small interfering RNA, chromatin immunoprecipitation, and transient transfection assays, we show that α-actinin 4 potentiates expression of TAF55, a putative MEF2 target gene. Loss of MEF2A interaction correlates with loss of the ability of α-actinin 4 to potentiate TAF55 promoter activity. Ectopic expression of α-actinin 4, but not the mutant defective in MEF2A association, leads to disruption of HDAC7·MEF2A association and enhancement of MEF2-mediated transcription. Taken together, we have identified a novel mechanism by which HDAC7 activity is negatively regulated and uncovered a previously unknown function of α-actinin 4.

Original languageEnglish (US)
Pages (from-to)35070-35080
Number of pages11
JournalJournal of Biological Chemistry
Volume281
Issue number46
DOIs
StatePublished - Nov 17 2006

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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