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

Bong Gun Ju, Derek Solum, Eun Joo Song, Kong Joo Lee, David W. Rose, Christopher K. Glass, Michael G. Rosenfeld

Research output: Contribution to journalArticlepeer-review

238 Scopus citations

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.

Original languageEnglish
Pages (from-to)815-829
Number of pages15
JournalCell
Volume119
Issue number6
DOIs
StatePublished - 17 Dec 2004

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