Abstract
In yeast cells, H2A.Z regulates transcription and is globally associated within a few nucleosomes of the initiator regions of numerous promoters. H2A.Z is deposited at these loci by an ATP-dependent complex, Swr1.com. Here we show that H2A.Z suppresses the p53 --> p21 transcription and senescence responses. Upon DNA damage, H2A.Z is first evicted from the p21 promoter, followed by the recruitment of the Tip60 histone acetyltransferase to activate p21 transcription. p400, a human Swr1 homolog, is required for the localization of H2A.Z, and largely colocalizes with H2A.Z at multiple promoters investigated. Notably, the presence of sequence-specific transcription factors, such as p53 and Myc, provides positioning cues that direct the location of H2A.Z-containing nucleosomes within these promoters. Collectively, this study strongly suggests that certain sequence-specific transcription factors regulate transcription, in part, by preferentially positioning histone variant H2A.Z within chromatin. This H2A.Z-centered process is part of an epigenetic process for modulating gene expression.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Binding Sites / genetics
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Cell Line
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Cells, Cultured
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Cellular Senescence
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Chromatin / genetics
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Chromatin / metabolism
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Cyclin-Dependent Kinase Inhibitor p21 / genetics*
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DNA Damage
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DNA Helicases / genetics
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DNA Helicases / metabolism
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DNA, Complementary / genetics
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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Epigenesis, Genetic
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Histone Acetyltransferases / metabolism
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Histones / metabolism*
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Humans
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Lysine Acetyltransferase 5
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Molecular Sequence Data
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Promoter Regions, Genetic
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Proto-Oncogene Proteins c-myc / metabolism
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Transcription, Genetic*
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Tumor Suppressor Protein p53 / deficiency
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism
Substances
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CDKN1A protein, human
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Chromatin
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Cyclin-Dependent Kinase Inhibitor p21
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DNA, Complementary
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DNA-Binding Proteins
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Histones
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MYC protein, human
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Proto-Oncogene Proteins c-myc
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TP53 protein, human
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Tumor Suppressor Protein p53
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histone H2A.F-Z
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Histone Acetyltransferases
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KAT5 protein, human
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Lysine Acetyltransferase 5
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DNA Helicases
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EP400 protein, human