Format

Send to

Choose Destination
Cell. 2004 Dec 17;119(6):815-29.

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

Author information

1
Howard Hughes Medical Institute, University of California, San Diego, Department and School of Medicine, La Jolla, CA 92093, USA.

Erratum in

  • Cell. 2006 Dec 16;127(6):1283.

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.

Comment in

PMID:
15607978
DOI:
10.1016/j.cell.2004.11.017
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center