Transcriptional regulation by p53 through intrinsic DNA/chromatin binding and site-directed cofactor recruitment.
The tumor suppressor protein, p53, plays a critical role in mediating cellular response to stress signals by regulating genes involved in cell cycle arrest and apoptosis. p53 is believed to be inactive for DNA binding unless its C terminus is modified or structurally altered. We show that unmodified p53 actively binds to two sites at -1.4 and -2.3 kb within the chromatin-assembled p21 promoter and requires the C terminus and the histone acetyltransferase, p300, for transcription. Acetylation of the C terminus by p300 is not necessary for binding or promoter activation. Instead, p300 acetylates p53-bound nucleosomes in the p21 promoter with spreading to the TATA box. Thus, p53 is an active DNA and chromatin binding protein that may selectively regulate its target genes by recruitment of specific cofactors to structurally distinct binding sites.
Espinosa
J M
JM
Regulatory Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Emerson
B M
BM
D000107:Acetylation; D000123:Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics* / Q000378:metabolism; D018983:DNA Footprinting; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics; D005786:Gene Expression Regulation; D006367:HeLa Cells; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor
D000123:Acetyltransferases; D018797:Cell Cycle Proteins; D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D051548:Histone Acetyltransferases; D006657:Histones; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor; C493956:CDKN1A protein, human