YY1 binding to a subset of p53 DNA-target sites regulates p53-dependent transcription.
The tumor suppressor protein p53 regulates gene transcription through binding to specific DNA-target sites. We here demonstrate that a subset of these sites is targeted by another DNA-binding factor. Binding specificity, reactivity with specific antibodies, and experiments with purified protein identified the factor as the multifunctional transcription regulator YY1. The YY1 core binding sequence ACAT is present in the center of p53-half-binding sites in the p21 and GADD45 genes regulating growth arrest and DNA repair, respectively, but is absent in those of the Bax gene critical for apoptosis. In transfection experiments YY1 inhibits p53-activated transcription from the p53-binding site that contains the ACAT sequence. YY1 and p53 are colocalized around the nucleoli and in discrete nuclear domains in PC12 cells undergoing apoptosis. YY1 might attenuate p53-dependent transcription from a subset of p53-target genes and this may be relevant for directing cells either to growth arrest or apoptosis upon p53 activation.
Yakovleva
Tatiana
T
Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Kolesnikova
Larissa
L
Vukojević
Vladana
V
Gileva
Irina
I
Tan-No
Koichi
K
Austen
Matthias
M
Lüscher
Bernhard
B
Ekström
Tomas J
TJ
Terenius
Lars
L
Bakalkin
Georgy
G
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D004247:DNA / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D024202:Electrophoretic Mobility Shift Assay; D050981:Erythroid-Specific DNA-Binding Factors; D006367:HeLa Cells; D006801:Humans; D009841:Oligonucleotides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016716:PC12 Cells; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays; D050986:YY1 Transcription Factor
D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D009841:Oligonucleotides; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D050986:YY1 Transcription Factor; C494698:YY1 protein, human; C494700:Yy1 protein, rat; D004247:DNA