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PMID: 15769944 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Regulation of neuron survival and death by p130 and associated chromatin modifiers.

Genes & development ·Vol. 19 ·No. 6 ·2005-03-15 ·Pages 719-32

Liu DX, Nath N, Chellappan SP, Greene LA

Abstract

E2F-mediated gene repression plays a key role in regulation of neuron survival and death. However, the key molecules involved in such regulation and the mechanisms by which they respond to apoptotic stimuli are largely unknown. Here we show that p130 is the predominant Rb family member associated with E2F in neurons, that its major partner for repression of pro-apoptotic genes is E2F4, and that the p130-E2F4 complex recruits the chromatin modifiers HDAC1 and Suv39H1 to promote gene silencing and neuron survival. Apoptotic stimuli induce neuron death by sequentially causing p130 hyperphosphorylation, dissociation of p130-E2F4-Suv39H1-HDAC complexes, altered modification of H3 histone and gene derepression. Experimental suppression of such events blocks neuron death while interference with the synthesis of E2F4 or p130, or with the interaction of E2F4-p130 with chromatin modifiers, induces neuron death. Thus, neuron survival and death are dependent on the integrity of E2F4-p130-HDAC/Suv39H1 complexes.

MeSH Terms
Animals Apoptosis/physiology Blotting, Western Cell Fractionation Cell Survival/physiology DNA-Binding Proteins/metabolism E2F4 Transcription Factor Electrophoretic Mobility Shift Assay Gene Silencing/physiology Histone Deacetylases/metabolism Histone-Lysine N-Methyltransferase/metabolism Immunoprecipitation Luciferases Neurons/metabolism,physiology PC12 Cells Phosphorylation Proteins/metabolism Rats Retinoblastoma-Like Protein p130 Transcription Factors/metabolism
Chemicals
DNA-Binding Proteins E2F4 Transcription Factor Proteins Rbl2 protein, rat Retinoblastoma-Like Protein p130 Transcription Factors Luciferases Histone-Lysine N-Methyltransferase Histone Deacetylases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Liu David X
Department of Pathology, Columbia University Medical Center, New York, New York 10032, USA. [email protected]
Nath Niharika
Chellappan Srikumar P
Greene Lloyd A
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1296405
Email
[email protected]
Published
2005-03-15
Pages
719-32
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC1065725
Subset
IM
External Links
PubMed source DOI: 10.1101/gad.1296405 PMC Full Text View journal details
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