Abstract
Profound chromatin changes occur during mitosis to allow for gene silencing and chromosome segregation followed by reactivation of memorized transcription states in daughter cells. Using genome-wide sequencing, we found H2A.Z-containing +1 nucleosomes of active genes shift upstream to occupy TSSs during mitosis, significantly reducing nucleosome-depleted regions. Single-molecule analysis confirmed nucleosome shifting and demonstrated that mitotic shifting is specific to active genes that are silenced during mitosis and, thus, is not seen on promoters, which are silenced by methylation or mitotically expressed genes. Using the GRP78 promoter as a model, we found H3K4 trimethylation is also maintained while other indicators of active chromatin are lost and expression is decreased. These key changes provide a potential mechanism for rapid silencing and reactivation of genes during the cell cycle.
Copyright © 2010 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
MeSH terms
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Acetylation
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CCAAT-Binding Factor / metabolism
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Cell Cycle Proteins / genetics
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Cell Division / genetics
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Cell Line, Tumor
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Chromatin Immunoprecipitation
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DNA Methylation / physiology
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DNA Polymerase II / metabolism
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Endoplasmic Reticulum Chaperone BiP
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G1 Phase / genetics
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Gene Expression / genetics
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Gene Silencing*
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Genes, p16 / physiology
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Heat-Shock Proteins / genetics
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Histones / metabolism*
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Humans
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Membrane Proteins / genetics
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Methylation
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Mitosis / genetics*
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Models, Genetic
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Nucleosomes / metabolism*
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Phosphorylation / physiology
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Polo-Like Kinase 1
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Promoter Regions, Genetic / physiology
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Protein Serine-Threonine Kinases / genetics
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Proto-Oncogene Proteins / genetics
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Resting Phase, Cell Cycle / genetics
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Sequence Analysis, DNA
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TATA-Box Binding Protein / metabolism
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Transcription Initiation Site / physiology
Substances
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CCAAT-Binding Factor
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Cell Cycle Proteins
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Endoplasmic Reticulum Chaperone BiP
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HSPA5 protein, human
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Heat-Shock Proteins
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Histones
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Membrane Proteins
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Nucleosomes
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Proto-Oncogene Proteins
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TATA-Box Binding Protein
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TBP protein, human
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histone H2A.F-Z
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wolframin protein
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Protein Serine-Threonine Kinases
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DNA Polymerase II