TY - JOUR
T1 - α-actinin 4 potentiates myocyte enhancer factor-2 transcription activity by antagonizing histone deacetylase 7
AU - Chakraborty, Sharmistha
AU - Reineke, Erin L.
AU - Lam, Minh
AU - Li, Xiaofang
AU - Liu, Yu
AU - Gao, Chengzhuo
AU - Khurana, Simran
AU - Kao, Hung Ying
PY - 2006/11/17
Y1 - 2006/11/17
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.M602474200
DO - 10.1074/jbc.M602474200
M3 - Article
C2 - 16980305
AN - SCOPUS:33845958654
SN - 0021-9258
VL - 281
SP - 35070
EP - 35080
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 46
ER -