Co-activation of atrial natriuretic factor promoter by Tip60 and serum response factor.
Tat-interactive protein 60 (Tip60) is a member of the MYST family of histone acetyltransferases (HATs). In addition to its HAT domain, Tip contains a heterochromatin-associated protein 1-like chromodomain and a zinc finger-like domain. Several alternative splice variants of Tip60 have been characterized, including full-length Tip60alpha, Tip60beta (which lacks exon V encoded by the Tip60 gene), and Tip55 (which encodes a novel 103-amino-acid C terminus). We report here that isoproteins recognized by a pan-Tip60 antibody are strongly and transiently expressed between embryonic days 8 and 11 in the embryonic mouse myocardium. A functional role for Tip60 isoproteins in cardiac myocyte differentiation is suggested by immunoprecipitation experiments showing that Tip60alpha, Tip60beta, and Tip55 can bind serum response factor (SRF) and by transient transfection assessments showing that Tip60 and SRF cooperatively activate the atrial natriuretic factor promoter. Although this combinatorial activity is inhibited by histone deacetylase 7, it was unexpectedly enhanced by point mutation of the HAT domain. Ablation of the chromodomain from Tip60beta caused derepression. These findings suggest that Tip60 modulates expression of SRF-dependent cardiac genes.
Kim
Min-Su
MS
Department of Cell Biology, Neurobiology, and Anatomy and the Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wisconsin 53226, USA.
Merlo
Xanthi
X
Wilson
Catherine
C
Lough
John
J
D000595:Amino Acid Sequence; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics* / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D004247:DNA / Q000235:genetics; D005318:Fetal Heart / Q000196:embryology / Q000378:metabolism; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism; D017354:Point Mutation; D011401:Promoter Regions, Genetic; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D011994:Recombinant Proteins; D026362:Serum Response Factor; D009320:Atrial Natriuretic Factor; D004247:DNA; D051548:Histone Acetyltransferases