RRC ID 1386
著者 Ju BG, Solum D, Song EJ, Lee KJ, Rose DW, Glass CK, Rosenfeld MG.
タイトル Activating the PARP-1 sensor component of the groucho/ TLE1 corepressor complex mediates a CaMKinase IIdelta-dependent neurogenic gene activation pathway.
ジャーナル Cell
Abstract Switching specific patterns of gene repression and activation in response to precise temporal/spatial signals is critical for normal development. Here we report a pathway in which induction of CaMKIIdelta triggers an unexpected switch in the function of the HES1 transcription factor from a TLE-dependent repressor to an activator required for neuronal differentiation. These events are based on activation of the poly(ADP-ribose) polymerase1 (PARP-1) sensor component of the groucho/TLE-corepressor complex mediating dismissal of the corepressor complex from HES1-regulated promoters. In parallel, CaMKIIdelta mediates a required phosphorylation of HES1 to permit neurogenic gene activation, revealing the ability of a specific signaling pathway to modulate both the derepression and the subsequent coactivator recruitment events required for transcriptional activation of a neurogenic program. The identification of PARP-1 as a regulated promoter-specific exchange factor required for activation of specific neurogenic gene programs is likely to be prototypic of similar molecular mechanisms.
巻・号 119(6)
ページ 815-29
公開日 2004-12-17
DOI 10.1016/j.cell.2004.11.017
PII S0092867404010931
PMID 15607978
MeSH Animals Basic Helix-Loop-Helix Transcription Factors Calcium-Calmodulin-Dependent Protein Kinases / metabolism* Cell Differentiation / physiology Cells, Cultured Chromatin Immunoprecipitation DNA-Binding Proteins / metabolism* Electrophoretic Mobility Shift Assay Enzyme Activation / physiology Gene Expression Regulation / physiology Homeodomain Proteins / metabolism Neurons / cytology Neurons / metabolism* Phosphorylation Poly(ADP-ribose) Polymerases / metabolism* Rats Repressor Proteins / metabolism* Stem Cells / cytology Stem Cells / metabolism Transcription Factor HES-1 Transcriptional Activation
IF 38.637
引用数 223
WOS 分野 BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
ヒト・動物細胞 10H