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PMID: 19596240 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Control of inducible gene expression by signal-dependent transcriptional elongation.

Cell ·Vol. 138 ·No. 1 ·2009-07-10 ·Pages 129-45

Hargreaves DC, Horng T, Medzhitov R

Abstract

Most inducible transcriptional programs consist of primary and secondary response genes (PRGs and SRGs) that differ in their kinetics of expression and in their requirements for new protein synthesis and chromatin remodeling. Here we show that many PRGs, in contrast to SRGs, have preassembled RNA polymerase II (Pol II) and positive histone modifications at their promoters in the basal state. Pol II at PRGs generates low levels of full-length unspliced transcripts but fails to make mature, protein-coding transcripts in the absence of stimulation. Induction of PRGs is controlled at the level of transcriptional elongation and mRNA processing, through the signal-dependent recruitment of P-TEFb. P-TEFb is in turn recruited by the bromodomain-containing protein Brd4, which detects H4K5/8/12Ac inducibly acquired at PRG promoters. Our findings suggest that the permissive structure of PRGs both stipulates their unique regulation in the basal state by corepressor complexes and enables their rapid induction in multiple cell types.

MeSH Terms
Animals Cell Line Chromatin Assembly and Disassembly Histone Code Histones/metabolism Humans Lipopolysaccharides/immunology,metabolism Macrophages/metabolism Mice Mice, Inbred C57BL Phosphorylation Protein Structure, Tertiary RNA Polymerase II/chemistry,metabolism Regulatory Sequences, Nucleic Acid Transcriptional Activation
Chemicals
Histones Lipopolysaccharides RNA Polymerase II
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Hargreaves Diana C
Howard Hughes Medical Institute and Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Horng Tiffany
Medzhitov Ruslan
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.05.047
Published
2009-07-10
Pages
129-45
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2828818
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NIAID NIH HHS · R37 AI046688 · United States
NIAID NIH HHS · R01 AI046688 · United States
NIAID NIH HHS · R37 AI046688-08 · United States
NIAID NIH HHS · U01 AI061360 · United States
Corrections
CommentIn
PMID: 19596228
External Links
PubMed source DOI: 10.1016/j.cell.2009.05.047 PMC Full Text View journal details
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