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

251 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

Bibliographical note

Funding Information:
We are very grateful to C. Nelson for excellent technical assistance; I. Bassets for gel filtration; V. Lunyak, P. Briata, L. Erkman, and V. Perissi for critical reading of the manuscript; and X. Zhu, R. McEvilly, and the other members of the Rosenfeld lab for discussions and valuable advice during the course of this study. We also thank Dr. R. Tsien for valuable discussion; R. Kageyama, D. Maiguel, and S.L. Oei for plasmids; J. Hightower and M. Fisher for figure and manuscript preparation; and M. Gonzalez (Santa Cruz Biotechnology) for advice on reagents. M.G.R. is an investigator with the Howard Hughes Medical Institute and B.J. is supported by USAMRMC (DAMD17-01-1-0184). T hese studies were supported by grants from Sander Programs for Asthma Research to M.G.R. and NIH to C.K.G, D.W.R., and M.G.R.

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