Bernard Lakowski | PubMed Health

PubMed2006

CoREST-like complexes regulate chromatin modification and neuronal gene expression.

The mammalian CoREST ([co]repressor for element-1-silencing transcription factor) complex was first identified associated with the repressor for element-1 silencing transcription factor (REST)/neuronal restrictive silencing factor. The CoREST complex is a chromatin-modifying corepressor complex that acts with REST to regulate neuronal gene expression and neuronal stem cell fate. Components of a CoREST-like complex have been identified recently in Xenopus laevis, Caenorhabditis elegans, and Drosophila melanogaster. Like the mammalian complex, the Drosophila complex is required to regulate neuronal gene expression, whereas the C. elegans homologs regulate the expression of the hop-1 presenilin gene, suggesting an ancient conserved function of CoREST complexes in regulating neuronal gene expression.

Animals↗

PubMed2003

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

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 C(2)H(2) 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.

Amino Acid Sequence↗