Biomedical subjects

Craig J Ceol

Publications and source records attributed to Craig J Ceol.

4 recordsLinked to original sources

PubMed2006

Some C. elegans class B synthetic multivulva proteins encode a conserved LIN-35 Rb-containing complex distinct from a NuRD-like complex.

The Caenorhabditis elegans synthetic multivulva (synMuv) genes act redundantly to antagonize the specification of vulval cell fates, which are promoted by an RTK/Ras pathway. At least 26 synMuv genes have been genetically identified, several of which encode proteins with homologs that act in chromatin remodeling or transcriptional repression. Here we report the molecular characterization of two synMuv genes, lin-37 and lin-54. We show that lin-37 and lin-54 encode proteins in a complex with at least seven synMuv proteins, including LIN-35, the only C. elegans homolog of the mammalian tumor suppressor Rb. Biochemical analyses of mutants suggest that LIN-9, LIN-53, and LIN-54 are required for the stable formation of this complex. This complex is distinct from a second complex of synMuv proteins with a composition similar to that of the mammalian Nucleosome Remodeling and Deacetylase complex. The class B synMuv complex we identified is evolutionarily conserved and likely functions in transcriptional repression and developmental regulation.

Animals↗

PubMed2006

Identification and classification of genes that act antagonistically to let-60 Ras signaling in Caenorhabditis elegans vulval development.

The synthetic multivulva (synMuv) genes negatively regulate Ras-mediated vulval induction in the nematode Caenorhabditis elegans. The synMuv genes define three classes, A, B, and C, such that double mutants carrying mutations in genes of any two classes are multivulva. The class B synMuv genes include lin-35, a homolog of the retinoblastoma (Rb) tumor suppressor gene, as well as homologs of genes that function with Rb in transcriptional regulation. We screened for additional synMuv mutations using a strategy different from that of previous synMuv genetic screens. Some of the mutations we recovered affect new synMuv genes. We present criteria for assigning synMuv mutations into different genetic classes. We also describe the molecular characterization of the class B synMuv gene lin-65.

Alleles↗

PubMed2004

A new class of C. elegans synMuv genes implicates a Tip60/NuA4-like HAT complex as a negative regulator of Ras signaling.

The class A and class B synMuv genes are functionally redundant negative regulators of a Ras signaling pathway that induces C. elegans vulval development. A number of class B synMuv genes encode components of an Rb and histone deacetylase complex that likely acts to repress transcription of genes required for vulval induction. We discovered a new class of synMuv genes that acts redundantly with both the A and B classes of genes in vulval cell-fate determination. These new class C synMuv genes encode TRRAP, MYST family histone acetyltransferase, and Enhancer of Polycomb homologs, which form a putative C. elegans Tip60/NuA4-like histone acetyltransferase complex. A fourth gene with partial class C synMuv properties encodes a homolog of the mammalian SWI/SNF family ATPase p400. Our findings indicate that the coordinated action of two chromatin-modifying complexes, one with histone deacetylase and the other with histone acetyltransferase activity, is important in regulating Ras signaling and specifying cell fates during C. elegans development.

Acetyltransferases↗

PubMed2003

New genes that interact with lin-35 Rb to negatively regulate the let-60 ras pathway in Caenorhabditis elegans.

Previous studies have shown that a synthetic multivulva phenotype results from mutations in genes that antagonize the ras-mediated intercellular signaling system responsible for vulval induction in Caenorhabditis elegans. Synthetic multivulva mutations define two classes of genes, A and B, and a mutation in a gene of each class is required to produce the multivulva phenotype. The ectopic vulval tissue in multivulva animals is generated by vulval precursor cells that in the wild type do not generate vulval tissue. One of the class B synthetic multivulva genes, lin-35, encodes a protein similar to the retinoblastoma (Rb) protein. In this article, we describe the isolation and characterization of 50 synthetic multivulva mutations, the identification of new components of both the class A and class B lin-35 Rb pathways, and the cloning of lin-52, a class B gene that may have a conserved role in Rb-mediated signaling.

Animals↗