Transcription regulatory networks in Caenorhabditis elegans

cyb-3 encodes a member of the cyclin B family that is required for embryonic viability, and may be involved with sister chromatid segregation.

cyd-1 encodes a cyclin D homolog that is required for escape from G1 cycle arrest in postembryonic blast cells, affects movement and larval viability, and may physically interact with CDK-46 and CKI-1; expressed embryonically primarily in the head, ventral cord, tail, and is later expressed primarily in the seam cells and in the somatic gonad.

cyn-4 encodes a divergent member of the cyclophilin family orthologous to human hCyP-60; in the hermaphrodite germline, cyn-4 activity is required for the sperm/oocyte switch, robust germline proliferation and, redundantly with gld-3, for the mitosis/meiosis decision; in addition, maternal cyn-4 is required for embryogenesis and loss of cyn-4 via RNAi results in morphological defects at early larval stages; in vitro, CYN-4 interacts with the MEP-1 NuRD complex component, as do the MOG-1, -4, and -5 proteins; CYN-4's interaction with MEP-1 is independent of the CYN-4 CBD (central binding domain) which is also dispensable for CYN-4's role in the sperm/oocyte switch; CYN-4 is expressed in the nuclei of both germline and somatic cells; in L4 larvae, CYN-4 is ubiquitously expressed in the mitotic and meiotic regions, but absent from the proximal zone.

cyn-6 encodes a cyclophilin most similar to human secreted cyclophilin type B isoforms that is functional when expressed in E. coli; it is expressed in the intestine.

cyn-9 encodes a peptidyl prolyl cis-trans isomerase most similar to human cyclophilin G (OMIM:606093); CYN-9 likely functions as a catalyst in the folding and modification of cuticle collagens; a cyn-9::lacZ reporter is expressed in the syncytial hypodermis from early larval through adult stages; cyn-9 mRNA is expressed most strongly at the mid-L3 and mid-L4 larval stages, the intermoult period when collagens are synthesized.

sig-7 encodes a predicted cyclophilin; loss of sig-7 activity via large-scale RNAi screens results in embryonic and larval lethality as well as reduced brood sizes, suggesting that SIG-7 plays an essential role during C. elegans development.

cyn-16 encodes a highly diverged member of the cyclophilin family; CYN-16 exhibits low levels of peptidyl-prolyl cis/trans isomerase activity in vitro that is insensitive to the presence of cyclosporin A; a cyn-16::gfp fusion protein is expressed in the intestine during larval and adult stages of development, with particularly strong expression seen in the anterior and posterior ends; in dauer larvae, the cyn-16::gfp reporter is expressed in cell bodies and processes of ventral cord neurons and is no longer visible in the intestine.

daf-2 encodes a predicted receptor tyrosine kinase that is the C. elegans insulin/IGF receptor ortholog; DAF-2 activity is required for a number of processes in C. elegans, including embryonic and larval development, formation of the developmentally arrested dauer larval stage, adult longevity, reproduction, fat storage, salt chemotaxis learning, and response to exogenous stressors such as high temperature or bacterial infection; DAF-2 signals through a conserved PI 3-kinase pathway to negatively regulate the activity of DAF-16, a Forkhead-related transcription factor, by inducing its phosphorylation and nuclear exclusion; in addition, DAF-2 negatively regulates the nuclear localization, and hence transcriptional activity, of SKN-1 in intestinal nuclei; amongst the 38 predicted insulin-like molecules in C. elegans, genetic and microarray analyses suggest that at least DAF-28, INS-1, and INS-7 are likely DAF-2 ligands; genetic mosaic and tissue-specific promoter studies indicate that daf-2 can function cell nonautonomously and within multiple cell types to influence dauer formation and adult lifespan, likely by regulating the production of secondary endocrine signals that coordinate growth and longevity throughout the animal.