Gene bookmarking accelerates the kinetics of post-mitotic transcriptional re-activation

Nat Cell Biol. 2011 Oct 9;13(11):1295-304. doi: 10.1038/ncb2341.

Abstract

Although transmission of the gene expression program from mother to daughter cells has been suggested to be mediated by gene bookmarking, the precise mechanism by which bookmarking mediates post-mitotic transcriptional re-activation has been unclear. Here, we used a real-time gene expression system to quantitatively demonstrate that transcriptional activation of the same genetic locus occurs with a significantly more rapid kinetics in post-mitotic cells versus interphase cells. RNA polymerase II large subunit (Pol II) and bromodomain protein 4 (BRD4) were recruited to the locus in a different sequential order on interphase initiation versus post-mitotic re-activation resulting from the recognition by BRD4 of increased levels of histone H4 Lys 5 acetylation (H4K5ac) on the previously activated locus. BRD4 accelerated the dynamics of messenger RNA synthesis by de-compacting chromatin and hence facilitating transcriptional re-activation. Using a real-time quantitative approach, we identified differences in the kinetics of transcriptional activation between interphase and post-mitotic cells that are mediated by a chromatin-based epigenetic mechanism.

Publication types

  • Research Support, American Recovery and Reinvestment Act
  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Acetylation
  • Cell Cycle Proteins / genetics*
  • Cell Cycle Proteins / metabolism
  • Cell Line, Tumor
  • Chromatin Assembly and Disassembly
  • Epigenesis, Genetic*
  • Gene Expression Regulation
  • Histones / genetics
  • Histones / metabolism
  • Humans
  • Interphase / genetics*
  • Kinetics
  • Lysine
  • Mitosis / genetics*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • RNA Polymerase II / genetics
  • RNA Polymerase II / metabolism
  • RNA, Messenger / biosynthesis*
  • Recombinant Fusion Proteins / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation*
  • Transfection

Substances

  • BRD4 protein, human
  • Cell Cycle Proteins
  • Histones
  • Nuclear Proteins
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Transcription Factors
  • RNA Polymerase II
  • Lysine