The synthetic multivulva genes and their suppressors regulate opposing cell fates through chromatin remodeling

The synthetic multivulva (synMuv) genes act redundantly to inhibit vulval fates in Caenorhabditis elegans. These genes are grouped into three classes called A, B and C. The class A genes encode putative transcription factors. The class B and C genes encode presumptive transcriptional repressors and chromatin-remodeling factors. The synMuv genes likely repress the transcription of the Ras pathway ligand lin-3 EGF. Some class B synMuv proteins are homologs of a Nucleosome Remodeling and Deacetylase (NuRD)-like complex and heterochromatin protein 1 (HP1). In addition to a NuRD-like complex, which deacetylates lysine nine of histone H3 (H3K9), and HP1, we found two histone methyltransferase (HMT) genes (met-1 and met-2) that act as class B synMuv genes and repress lin-3 transcription. met-1 encodes a C. elegans homolog of yeast Set2, an H3K36 HMT that inhibits the ectopic initiation of transcription, and met-2 encodes a homolog of human SETDB1, an H3K9 HMT involved in transcriptional repression. Our results link H3K36 methylation to a transcriptional repression cascade composed of the NuRD complex, H3K9 methylation and HP1 in the inhibition of ectopic transcriptional initiation. We found that not only do the class A and B synMuv genes act redundantly to inhibit vulval fates, but most genes within each class act in parallel. Pairs of genes, which act together biochemically, function in a single activity in vulval cell-fate specification. Our findings offer an opportunity to determine molecular activities for uncharacterized but conserved synMuv proteins.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Biology.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2008

Author dc:creator

• Andersen, Erik C

Advisor dc:contributor.advisor

• H. Robert Horvitz.

• Biology.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/42072

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/42072