gon-14 Functions With Class B and Class C Synthetic Multivulva Genes to Control Larval Growth in Caenorhabditis elegans

Abstract

Previous work showed that C. elegans gon-14 is required for gonadogenesis. Here we report that gon-14 encodes a protein with similarity to LIN-15B, a class B synMuv protein. An extensive region of GON-14 contains blocks of sequence similarity to transposases of the hAT superfamily, but key residues are not conserved, suggesting a distant relationship. GON-14 also contains a putative THAP DNA-binding domain. A rescuing gon-14TGON-14TVENUS reporter is broadly expressed during development and localizes to the nucleus. Strong loss-of-function and predicted null gon-14 alleles have pleiotropic defects, including multivulval (Muv) defects and temperature-sensitive larval arrest. Although the gon-14 Muv defect is not enhanced by synMuv mutations, gon-14 interacts genetically with class B and class C synMuv genes, including lin-35/Rb, let-418/Mi-2b, and trr-1/TRRAP. The gon-14; synMuv double mutants arrest as larvae when grown under conditions supporting development to adulthood for the respective single mutants. The gon-14 larval arrest is suppressed by loss of mes-2/E(Z), mes-6/ESC, or mes-4, which encodes a SET domain protein. Additionally, gon-14 affects expression of pgl-1 and lag-2, two genes regulated by the synMuv genes. We suggest that gon-14 functions with class B and class C synMuv genes to promote larval growth, in part by antagonizing MES-2,3,6/ESC-E(z) and MES-4.

Structure-Function Analysis of the THAP Zinc Finger of THAP1, a Large C2CH DNA-binding Module Linked to Rb/E2F Pathways

“…Indeed, in zebra fish and other fish species, the ortholog of cell cycle transcription factor E2F6, a repressor of E2F-dependent transcription during S phase (11) was found to contain a THAP zinc finger at its N terminus (7). In the nematode Caenorhabditis elegans, five distinct THAP zinc finger proteins (LIN-36, LIN-15B, LIN-15A, HIM-17, and GON-14) (7) were shown to interact genetically with LIN-35/ Rb, the sole C. elegans retinoblastoma homolog (12)(13)(14)(15)(16). Among these, GON-14 appeared to function as a positive regulator of cell proliferation, because cell division defects were observed in the intestine, gonad, and vulva of gon-14 null mutant (16).…”

“…In the nematode Caenorhabditis elegans, five distinct THAP zinc finger proteins (LIN-36, LIN-15B, LIN-15A, HIM-17, and GON-14) (7) were shown to interact genetically with LIN-35/ Rb, the sole C. elegans retinoblastoma homolog (12)(13)(14)(15)(16). Among these, GON-14 appeared to function as a positive regulator of cell proliferation, because cell division defects were observed in the intestine, gonad, and vulva of gon-14 null mutant (16). In contrast, LIN-36 and LIN-15B, initially characterized for their role in the specification of vulval cell fates (synthetic Multivulva class B genes, synMuvB) (12,13), were found to function as inhibitors of the G 1 /S cell cycle transition (14).…”

A Role forCaenorhabditis elegansChromatin-Associated Protein HIM-17 in the Proliferationvs. Meiotic Entry Decision

“…We first identified HIM-17 on the basis of its role in meiotic recombination (Reddy and Villeneuve 2004). HIM-17 is associated with chromatin throughout the germline and is a modular protein containing six repeats of a putative DNA-binding motif also found in several other proteins implicated in chromatin regulation through genetic interactions with LIN-35/Rb (Ferguson and Horvitz 1989;Clark et al 1994;Thomasand Horvitz 1999;Chesney et al 2006). Under standard conditions (20°), him-17 mutants exhibit normal pairing and synapsis but have reduced or delayed DSB formation, leading to a deficit of crossovers and chiasmata.…”

Ronin and Caspases in Embryonic Stem Cells: A New Perspective on Regulation of the Pluripotent State

“…The human genome contains 12 THAP-domain-containing proteins, of which only DAP4/p52rIPK, THAP1, and THAP7 have been characterized in detail (the mouse genome contains five THAPdomain-containing proteins). Caenorhabditis elegans expresses several important THAP proteins, including Lin-15b (Chesney et al 2006) and Lin-36 (encoded by the class-B synthetic multivulva genes) (Clouaire et al 2005), CDC-14B and CTB-1 (an ortholog of CtBP-1), all of which are involved in transcriptional control, and the protein HIM-17 (Reddy and Villeneuve 2004), which is involved in meiotic recombination and recruitment of the methyltransferase activity of histone H3 at lysine 9. Evidence for active DNA transposons containing a THAP domain has been obtained in zebra fish, and it is clear that this class of transposons was "domesticated" in a common ancestor of birds and mammals (Hammer et al 2005;Quesneville et al 2005).…”