spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

doi: 10.1242/10.1242/dev.00429

This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Data
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lakowski, B.
Right arrow Articles by Baumeister, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lakowski, B.
Right arrow Articles by Baumeister, R.
Development 130, 2117-2128 (2003)
Copyright © 2003 The Company of Biologists Limited

Two suppressors of sel-12 encode C2H2 zinc-finger proteins that regulate presenilin transcription in Caenorhabditis elegans

Bernard Lakowski*, Stefan Eimer, Christine Göbel, Andreas Böttcher, Babett Wagler and Ralf Baumeister{dagger}

ABI, Department of Biochemistry, Laboratory of Molecular Neurogenetics, Ludwig-Maximilians-Universitaet, Schillerstr. 44, D-80336 Munich, Germany
* Present address: Department of Neuroscience, Pasteur Institute, Paris, France

{dagger} Author for correspondence (e-mail: ralf.baumeister{at}pbm.med.uni-muenchen.de)

Accepted 3 February 2003

Mutations in presenilin genes are associated with familial Alzheimer's disease in humans and affect LIN-12/Notch signaling in all organisms tested so far. Loss of sel-12 presenilin activity in Caenorhabditis elegans results in a completely penetrant egg-laying defect. In screens for extragenic suppressors of the sel-12 egg-laying defect, we have isolated mutations in at least five genes. We report the cloning and characterization of spr-3 and spr-4, which encode large basic C2H2 zinc-finger proteins. Suppression of sel-12 by spr-3 and spr-4 requires the activity of the second presenilin gene, hop-1. Mutations in both spr-3 and spr-4 de-repress hop-1 transcription in the early larval stages when hop-1 expression is normally nearly undetectable. As sel-12 and hop-1 are functionally redundant, this suggests that mutations in spr-3 and spr-4 bypass the need for one presenilin by stage-specifically de-repressing the transcription of the other. Both spr-3 and spr-4 code for proteins similar to the human REST/NRSF (Re1 silencing transcription factor/neural-restrictive silencing factor) transcriptional repressors. As other Spr genes encode proteins homologous to components of the CoREST co-repressor complex that interacts with REST, and the INHAT (inhibitor of acetyltransferase) co-repressor complex, our data suggest that all Spr genes may function through the same mechanism that involves transcriptional repression of the hop-1 locus.

Key words: Presenilin, Alzheimer's disease, Genetic suppression, Transcription regulation




This article has been cited by other articles:


Home page
 Genome Res.Home page
A. Mortazavi, E. C. L. Thompson, S. T. Garcia, R. M. Myers, and B. Wold
Comparative genomics modeling of the NRSF/REST repressor network: From single conserved sites to genome-wide repertoire
Genome Res., October 1, 2006; 16(10): 1208 - 1221.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2003