Shuttling of HDAC5 in H9C2 cells regulates YY1 function through CaMKIV/PKD and PP2A.
YY1 is a transcription factor that can activate or repress transcription of a variety of genes and is involved in several developmental processes. YY1 is a repressor of transcription in differentiated H9C2 cells and in neonatal cardiac myocytes but an activator of transcription in undifferentiated H9C2 cells. We now present a detailed analysis of the functional domains of YY1 when it is acting as a repressor or an activator and identify the mechanism whereby its function is regulated in the differentiation of H9C2 cells. We show that histone deacetylase 5 (HDAC5) is localized to the cytoplasm in undifferentiated H9C2 cells and that this localization is dependent on Ca(2+)/calmodulin-dependent kinase IV (CaMKIV) and/or protein kinase D (PKD). In differentiated cells, HDAC5 is nuclear and interacts with YY1. Finally, we show that HDAC5 localization in differentiated cells is dependent on phosphatase 2A (PP2A). Our results suggest that a signaling mechanism that involves CaMKIV/PKD and PP2A controls YY1 function through regulation of HDAC5 and is important in the maintenance of muscle differentiation.
Sucharov
Carmen C
CC
Division of Cardiology, School of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA. kika.sucharov@uchsc.edu
Langer
Stephen
S
Bristow
Michael
M
Leinwand
Leslie
L
D000818:Animals; D000831:Animals, Newborn; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; D002227:Carbazoles / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006352:Heart Ventricles / Q000166:cytology; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D026121:Indole Alkaloids; D032383:Myocytes, Cardiac / Q000166:cytology*; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism*; D054648:Protein Phosphatase 2; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D050986:YY1 Transcription Factor / Q000737:chemistry / Q000378:metabolism*
D002227:Carbazoles; D026121:Indole Alkaloids; D050986:YY1 Transcription Factor; C049985:staurosporine aglycone; D011494:Protein Kinases; C089212:protein kinase D; D011493:Protein Kinase C; C517683:CAMK4 protein, human; D054734:Calcium-Calmodulin-Dependent Protein Kinase Type 4; C517686:Camk4 protein, rat; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2; D006655:Histone Deacetylases