Transcription regulatory networks in Caenorhabditis elegans

daf-8 encodes a Smad protein that represses dauer development, perhaps by antagonizing DAF-3 activity, and promotes a commitment to reproductive growth; genetic interactions suggest partial functional redundancy with daf-14 with respect to the TGF-beta signaling pathway that regulates dauer formation.

daf-14 encodes a Smad-related protein that is unusual in that while its C-terminus is well-conserved with Smad proteins, it lacks the N-terminal DNA binding domain found in all other known Smads; DAF-14 is predicted to function as a transducer of the DAF-7/TGF-beta-mediated signal that promotes reproductive growth and negatively regulates dauer formation; as reduction of daf-14 function enhances the dauer constitutive phenotype of daf-8 mutants, and overexpression of daf-14 can rescue daf-8 mutant animals, it is likely that the DAF-14 and DAF-8 Smad proteins function in parallel to control dauer formation; further genetic analyses suggest that DAF-14 and DAF-8 function to antagonize the activities of the DAF-3 Smad and DAF-5 Sno/Ski oncoprotein, which are required for dauer formation; a DAF-14::GFP reporter is expressed in a dynamic pattern in tissues, such as the hypodermis, intestine, and pharynx, that are remodeled during dauer development.

dao-2 encodes a (putatively) secreted protein with a DB module; dao-2 is down-regulated in daf-2 mutant adults by comparison with normal adults, and thus may be involved in dauer formation.

daz-1 encodes a protein containing an RNA recognition motif that is required for the progression of meiosis during oogenesis; DAZ-1 is expressed in the germline, and expression levels peak in the proximal pachytene region; cpb-3(bt17);daz-1(tj3) hermaphrodites have a synthetic phenotype of total sterility and masculinization; DAZ-1 colocalizes with CPB-3 in vivo, coimmunoprecipitates with CPB-3, and binds CPB-3 in two-hybrid assays.

ddp-1 encodes the C. elegans ortholog of Saccharomyces cerevisiae Tim8p and human deafness/dystonia peptide (DDP; OMIM:300356, mutated in Mohr-Tranebjaerg syndrome); by homology, DDP-1 is predicted to be part of a heterooligomeric complex that localizes to the mitochondrial intermembrane space and facilitates translocation of proteins from the cytosol to the inner mitochondrial membrane; loss of ddp-1 activity via large-scale RNAi screens does not result in any obvious abnormalities, indicating that ddp-1 is not essential for C. elegans development or may function redundantly with its paralogs, TIN-9, -10, and -13.

dgk-2 encodes a putative diacylglycerol kinase.

dhc-1 encodes a cytoplasmic dynein heavy chain homolog required in one-cell embryos for pronuclear migration, centrosome separation, centrosome proximity to the male pronucleus, and mitotic spindle orientation, suggesting that DHC-1 helps position the microtubule organizing center; DHC-1 genetically interacts with SPD-5, a coiled-coil centrosomal protein.

dhs-3 encodes a member of the short-chain dehydrogenases/reductases family (SDR) predicted to be mitochondrial.

The dhs-6 locus is predicted to encode four transcripts derived from alternative splicing and alternative transcriptional initiation sites; the longest transcript is predicted to encode a member of the eukaryotic translation initiation factor family within its amino-terminal end, and is a member of both the SCP-2 sterol transfer family and short-chain dehydrogenase-reductase families within its carboxyl-terminal end; DHS-6 is predicted to be mitochondrial.