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Activating the PARP-1 sensor component of the groucho/ TLE1 corepressor complex mediates a CaMKinase IIδ-dependent neurogenic gene activation pathway

Title
Activating the PARP-1 sensor component of the groucho/ TLE1 corepressor complex mediates a CaMKinase IIδ-dependent neurogenic gene activation pathway
Authors
Ju B.-G.Solum D.Song E.J.Lee K.-J.Rose D.W.Glass C.K.Rosenfeld M.G.
Ewha Authors
이공주
SCOPUS Author ID
이공주scopus
Issue Date
2004
Journal Title
Cell
ISSN
0092-8674JCR Link
Citation
Cell vol. 119, no. 6, pp. 815 - 829
Indexed
SCI; SCIE; SCOPUS WOS scopus
Document Type
Article
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 CaMKIIδ 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, CaMKIIδ 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.
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DOI
10.1016/j.cell.2004.11.017
Appears in Collections:
약학대학 > 약학과 > Journal papers
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