TY - JOUR
T1 - Deacetylase recruitment by the C/H3 domain of the acetyltransferase p300
AU - Simone, Cristiano
AU - Stiegler, Peter
AU - Forcales, Sonia Vanina
AU - Bagella, Luigi
AU - De Luca, Antonio
AU - Sartorelli, Vittorio
AU - Giordano, Antonio
AU - Puri, Pier Lorenzo
PY - 2004/3/18
Y1 - 2004/3/18
N2 - The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the acetyltransferase p300 and histone deacetylases. The C/H3 region of p300 was found to co-purify deacetylase activity from nuclear cell extracts. A prototype of class I histone deacetylases, HDAC1, interacts with p300 C/H3 domain in vitro and in vivo. The p300-binding protein E1A competes with HDAC1 for C/H3 binding; and, like E1A, HDAC1 overexpression interferes with either activation of Ga14p300 fusion protein or p300-dependent co-activation of two C/H3-binding proteins, MyoD and p53. The exposure to deacetylase inhibitors could reverse the dominant-negative effect of a C/H3 fragment insulated from the rest of the molecule, on MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to trichostatin A. These data support the hypothesis that association between acetyltransferases and deacetylases can control the expression of genes implicated in cellular growth and differentiation, and suggest that the dominant-negative effect of the p300 C/H3 fragment relies on deacetylase recruitment.
AB - The balance between acetylation and deacetylation of histone and nonhistone proteins controls gene expression in a variety of cellular processes, with transcription being activated by acetyltransferases and silenced by deacetylases. We report here the formation and enzymatic characterization of a complex between the acetyltransferase p300 and histone deacetylases. The C/H3 region of p300 was found to co-purify deacetylase activity from nuclear cell extracts. A prototype of class I histone deacetylases, HDAC1, interacts with p300 C/H3 domain in vitro and in vivo. The p300-binding protein E1A competes with HDAC1 for C/H3 binding; and, like E1A, HDAC1 overexpression interferes with either activation of Ga14p300 fusion protein or p300-dependent co-activation of two C/H3-binding proteins, MyoD and p53. The exposure to deacetylase inhibitors could reverse the dominant-negative effect of a C/H3 fragment insulated from the rest of the molecule, on MyoD- and p53-dependent transcription, whereas inhibition by E1A was resistant to trichostatin A. These data support the hypothesis that association between acetyltransferases and deacetylases can control the expression of genes implicated in cellular growth and differentiation, and suggest that the dominant-negative effect of the p300 C/H3 fragment relies on deacetylase recruitment.
KW - Acetyltransferases
KW - Deacetylases
KW - HDAC
KW - p300
KW - Transcription
UR - http://www.scopus.com/inward/record.url?scp=1842591163&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842591163&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1207327
DO - 10.1038/sj.onc.1207327
M3 - Article
C2 - 14968110
AN - SCOPUS:1842591163
VL - 23
SP - 2177
EP - 2187
JO - Oncogene
JF - Oncogene
SN - 0950-9232
IS - 12
ER -