H2A.Z maintenance during mitosis reveals nucleosome shifting on mitotically silenced genes

Mol Cell. 2010 Sep 24;39(6):901-11. doi: 10.1016/j.molcel.2010.08.026.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acetylation
  • CCAAT-Binding Factor / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Division / genetics
  • Cell Line, Tumor
  • Chromatin Immunoprecipitation
  • DNA Methylation / physiology
  • DNA Polymerase II / metabolism
  • G1 Phase / genetics
  • Gene Expression / genetics
  • Gene Silencing*
  • Genes, p16 / physiology
  • Heat-Shock Proteins / genetics
  • Histones / metabolism*
  • Humans
  • Membrane Proteins / genetics
  • Methylation
  • Mitosis / genetics*
  • Models, Genetic
  • Nucleosomes / metabolism*
  • Phosphorylation / physiology
  • Promoter Regions, Genetic / physiology
  • Protein-Serine-Threonine Kinases / genetics
  • Proto-Oncogene Proteins / genetics
  • Resting Phase, Cell Cycle / genetics
  • Sequence Analysis, DNA
  • TATA-Box Binding Protein / metabolism
  • Transcription Initiation Site / physiology

Substances

  • CCAAT-Binding Factor
  • Cell Cycle Proteins
  • Heat-Shock Proteins
  • Histones
  • Membrane Proteins
  • Nucleosomes
  • Proto-Oncogene Proteins
  • TATA-Box Binding Protein
  • TBP protein, human
  • histone H2A.F-Z
  • wolframin protein
  • Protein-Serine-Threonine Kinases
  • polo-like kinase 1
  • DNA Polymerase II
  • molecular chaperone GRP78

Associated data

  • GEO/GSE19568