Academic journal article Genetics

Gon-14 Functions with Class B and Class C Synthetic Multivulva Genes to Control Larval Growth in Caenorhabditis Elegans

Academic journal article Genetics

Gon-14 Functions with Class B and Class C Synthetic Multivulva Genes to Control Larval Growth in Caenorhabditis Elegans

Article excerpt

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-14::GON-14::VENUS 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-2β, 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.

CHROMATIN structure can influence a broad range of biologically important processes, such as transcription, DNA replication, DNA damage repair, and homologous recombination. The structure of chromatin is modulated by post-translational modifications to the N-terminal tails of histones and by the activity of chromatin remodeling factors (reviewed in JENUWEIN and ALLIS 2001; BECKER and HORZ 2002). Although considerable progress has been made in identifying biochemical and genetic pathways that regulate chromatin structure, much remains unknown regarding how these pathways are utilized to control development.

Caenorhabditis elegans vulval development has emerged as a model for analyzing the chromatin regulation of specific cell fate decisions. Vulval development is positively regulated by an RTK/Ras signaling pathway and antagonized by the synthetic Multivulva (synMuv) genes, which encode homologs of transcriptional regulators and chromatin remodeling factors (reviewed in FAY and HAN 2000; LIPSICK 2004). The synMuv genes fall into at least three classes, A, B, and C, which act redundantly to control cell fate specification in six ectodermal blast cells called the vulval precursor cells (VPCs) (FERGUSON and HORVITZ 1989; CEOL and HORVITZ 2004). In wildtype animals, three VPCs are induced to the vulval fate, while the three others assume a hypodermal fate (SULSTON and HORVITZ 1977). Single mutants of class A or class B synMuv genes typically exhibit normal VPC specification; however, in double mutants lacking one class A gene and one class B gene, all six VPCs adopt vulval fates, a defect called synMuv (HoRViTZ and SULSTON 1980; FERGUSON and HORVITZ 1989). Class C synMuv genes function redundantly in VPC specification with both class A and class B genes (CEOL and HORVITZ 2004).

Most relevant to this work are the class B synMuv genes, some of which encode nematode homologs of components integral to the vertebrate E2F-retinoMastoma (E2FRb) and NuRD (wMcleosome remodeling and histone ifeacetylation) complexes (reviewed in FAY and HAN 2000; LIPSICK 2004). Studies in various organisms indicate that the E2F-Rb complex represses transcription of E2F target genes and cell cycle progression, in part by recruiting chromatin-modifying proteins such as histone deacetylases (HDACs) (reviewed in FROLOV and DYSON 2004). Experiments with Drosophila embryos revealed that homologs of many class B synMuv proteins are physically associated in larger E2F- and Rb-containing complexes, known as /Jrosophila /?BF, d£2F2, end dAiyb-interacting proteins (dREAM) and Myb-synMuvB (Myb-MuvB); both complexes contain homologs of class B synMuv proteins LIN-35/Rb, EFL-1/E2F2, DPL-l/DP, LIN-9/ Mipl30/TWIT, LIN-37/Mip40, LIN-53/RbAp48, and LIN-54/Mipl20, while the Myb-MuvB complex includes the additional class B homologs HDA-1/RPD3/HDAC, LIN-61/L(3)MBT, and LIN-52/dLIN-52 (KORENJAK et al 2004; LEWIS et al 2004). …

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