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PMID: 21983563 Published · epublish English Journal Article Research Support, American Recovery and Reinvestment Act Research Support, N.I.H., Extramural Video-Audio Media

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

Nature cell biology ·Vol. 13 ·No. 11 ·2011-10-09 ·Pages 1295-304

Zhao R, Nakamura T, Fu Y, Lazar Z, Spector DL

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.

MeSH Terms
Acetylation Cell Cycle Proteins/genetics,metabolism Cell Line, Tumor Chromatin Assembly and Disassembly Epigenesis, Genetic Gene Expression Regulation Histones/genetics,metabolism Humans Interphase/genetics Kinetics Lysine Mitosis/genetics Nuclear Proteins/genetics,metabolism RNA Polymerase II/genetics,metabolism RNA, Messenger/biosynthesis Recombinant Fusion Proteins/metabolism Transcription Factors/genetics,metabolism Transcriptional Activation Transfection
Chemicals
BRD4 protein, human Cell Cycle Proteins Histones Nuclear Proteins RNA, Messenger Recombinant Fusion Proteins Transcription Factors RNA Polymerase II Lysine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Zhao Rui
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, New York 11724, USA.
Nakamura Tetsuya
Fu Yu
Lazar Zsolt
Spector David L
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Article Info
Journal
Nature cell biology
Abbr.
Nat Cell Biol
ISSN
1476-4679
DOI
10.1038/ncb2341
Published
2011-10-09
Epub
2011-00-09
Pages
1295-304
Language
English
Region
England
NLM ID
100890575
PMCID
PMC3210065
Subset
IM
Grants
PHS HHS · 42694 · United States
NIGMS NIH HHS · R01 GM042694-22 · United States
NIGMS NIH HHS · R01 GM042694-21 · United States
NIGMS NIH HHS · R01 GM042694-20S1 · United States
NIGMS NIH HHS · R01 GM042694 · United States
NIGMS NIH HHS · R01 GM042694-20 · United States
PHS HHS · 42694-2OS1 · United States
Corrections
CommentIn
PMID: 22075142
External Links
PubMed source DOI: 10.1038/ncb2341 PMC Full Text View journal details
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