Caenorhabditis elegans
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PROVIDER: PRJNA153929 | ENA |
REPOSITORIES: ENA
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Project description:This SuperSeries is composed of the following subset Series: GSE28494: Germline and embryo gene expression of wild-type vs. mutants in lin-54, a component of the C. elegans DRM complex GSE28852: Chromosome-biased binding and gene reguation by the C. elegans DRM complex [ChIP-chip] Refer to individual Series
2011-04-27 | E-GEOD-28853 | BioStudies
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we describe new aspects of DRM binding and function revealed through genome-wide analyses of the Caenorhabditis elegans DRM subunit LIN-54. We show that LIN-54 DNA-binding activity recruits DRM to promoters enriched for adjacent putative E2F/DP and LIN-54 binding sites, suggesting that these two DNA-binding moieties together direct DRM to its target genes. Chromatin immunoprecipitation and gene expression profiling reveals conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find that LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, C. elegans DRM does not act uniformly throughout the genome: the DRM recruitment motif, DRM binding, and DRM-regulated embryonic genes are all under-represented on the X chromosome. However, germline genes down-regulated in lin-54 mutants are over-represented on the X chromosome. We discuss models for how loss of autosome-bound DRM may enhance germline X chromosome silencing. We propose that autosome-enriched binding of DRM arose in C. elegans as a consequence of germline X chromosome silencing and the evolutionary redistribution of germline-expressed and essential target genes to autosomes. Sex chromosome gene regulation may thus have profound evolutionary effects on genome organization and transcriptional regulatory networks.
2011-01-01 | S-EPMC3093354 | BioStudies
Project description:This SuperSeries is composed of the following subset Series: GSE28494: Germline and embryo gene expression of wild-type vs. mutants in lin-54, a component of the C. elegans DRM complex GSE28852: Chromosome-biased binding and gene reguation by the C. elegans DRM complex [ChIP-chip] Refer to individual Series
2011-04-27 | E-GEOD-28853 | ArrayExpress
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we perform microarray expression profiling analysis of lin-54, a DNA-binding member of the DRM complex. To identify genes regulated by LIN-54 in soma and germline, we analyzed wild-type and lin-54 mutant C. elegans embryos and isolated germlines. We chose embryos because they consist primarily of somatic cells, at a developmental stage with both active cell divisions and dynamic developmental gene expression programs. Since lin-54 null animals are sterile, embryos were obtained from a strain carrying the partial loss-of-function allele lin-54(n2990). Germlines were dissected from lin-54(n3423) null adults that lack detectable transcript and protein. The results revealed conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, genomics and cytological analyses show that DRM binding, a DRM binding motif, and LIN-54-regulated genes are all autosome-enriched. One paradoxical exception occurs the germline, where DRM binds autosomes but genes down-regulated in DRM mutants are enriched on X chromosomes. We compared embryonic or germline gene expression profile of lin-54 mutants with that of wild-type N2 C. elegans. Embryos were obtained from a strain carrying the partial loss-of-function allele lin-54(n2990) grown at 25C for one generation. Germlines were isolated from lin-54(n3423) null adults that lack detectable lin-54 transcript and protein. We isolated the germline region from the tip until late pachytene stage of meiosis, because nuclei in this region are morphologically similar between wild-type and mutant and are all undergoing X chromosome silencing. 3 biological replicates of each genotype/tissue were examined.
2011-04-09 | E-GEOD-28494 | BioStudies
Project description:During animal development, gene transcription is tuned to tissue-appropriate levels. Here we uncover antagonistic regulation of transcript levels in the germline of Caenorhabditis elegans hermaphrodites. The histone methyltransferase MES-4 (Maternal Effect Sterile-4) marks genes expressed in the germline with methylated lysine on histone H3 (H3K36me) and promotes their transcription; MES-4 also represses genes normally expressed in somatic cells and genes on the X chromosome. The DRM transcription factor complex, named for its Dp/E2F, Retinoblastoma-like, and MuvB subunits, affects germline gene expression and prevents excessive repression of X-chromosome genes. Using genome-scale analyses of germline tissue, we show that common germline-expressed genes are activated by MES-4 and repressed by DRM, and that MES-4 and DRM co-bind many germline-expressed genes. Reciprocally, MES-4 represses and DRM activates a set of autosomal soma-expressed genes and overall X-chromosome gene expression. Mutations in mes-4 and the DRM subunit lin-54 oppositely skew the transcript levels of their common targets and cause sterility. A double mutant restores target gene transcript levels closer to wild type, and the concomitant loss of lin-54 suppresses the severe germline proliferation defect observed in mes-4 single mutants. Together, "yin-yang" regulation by MES-4 and DRM ensures transcript levels appropriate for germ-cell function, elicits robust but not excessive dampening of X-chromosome-wide transcription, and may poise genes for future expression changes. Our study reveals that conserved transcriptional regulators implicated in development and cancer counteract each other to fine-tune transcript dosage.
2014-01-01 | S-EPMC3887530 | BioStudies
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we perform microarray expression profiling analysis of lin-54, a DNA-binding member of the DRM complex. To identify genes regulated by LIN-54 in soma and germline, we analyzed wild-type and lin-54 mutant C. elegans embryos and isolated germlines. We chose embryos because they consist primarily of somatic cells, at a developmental stage with both active cell divisions and dynamic developmental gene expression programs. Since lin-54 null animals are sterile, embryos were obtained from a strain carrying the partial loss-of-function allele lin-54(n2990). Germlines were dissected from lin-54(n3423) null adults that lack detectable transcript and protein. The results revealed conserved roles for DRM in regulating genes involved in cell division, development, and reproduction. We find LIN-54 promotes expression of reproduction genes in the germline, but prevents ectopic activation of germline-specific genes in embryonic soma. Strikingly, genomics and cytological analyses show that DRM binding, a DRM binding motif, and LIN-54-regulated genes are all autosome-enriched. One paradoxical exception occurs the germline, where DRM binds autosomes but genes down-regulated in DRM mutants are enriched on X chromosomes. We compared embryonic or germline gene expression profile of lin-54 mutants with that of wild-type N2 C. elegans. Embryos were obtained from a strain carrying the partial loss-of-function allele lin-54(n2990) grown at 25C for one generation. Germlines were isolated from lin-54(n3423) null adults that lack detectable lin-54 transcript and protein. We isolated the germline region from the tip until late pachytene stage of meiosis, because nuclei in this region are morphologically similar between wild-type and mutant and are all undergoing X chromosome silencing. 3 biological replicates of each genotype/tissue were examined.
2011-04-09 | E-GEOD-28494 | ArrayExpress
Project description:The mechanisms controlling cell fate determination and reprogramming are fundamental for development. A profound reprogramming, allowing the production of pluripotent cells in early embryos, takes place during the oocyte-to-embryo transition. To understand how the oocyte reprogramming potential is controlled, we sought Caenorhabditis elegans mutants in which embryonic transcription is initiated precociously in germ cells. This screen identified LIN-41, a TRIM-NHL protein and a component of the somatic heterochronic pathway, as a temporal regulator of pluripotency in the germline. We found that LIN-41 is expressed in the cytoplasm of developing oocytes, which, in lin-41 mutants, acquire pluripotent characteristics of embryonic cells and form teratomas. To understand LIN-41 function in the germline, we conducted structure-function studies. In contrast to other TRIM-NHL proteins, we found that LIN-41 is unlikely to function as an E3 ubiquitin ligase. Similar to other TRIM-NHL proteins, the somatic function of LIN-41 is thought to involve mRNA regulation. Surprisingly, we found that mutations predicted to disrupt the association of LIN-41 with mRNA, which otherwise compromise LIN-41 function in the heterochronic pathway in the soma, have only minor effects in the germline. Similarly, LIN-41-mediated repression of a key somatic mRNA target is dispensable for the germline function. Thus, LIN-41 appears to function in the germline and the soma via different molecular mechanisms. These studies provide the first insight into the mechanism inhibiting the onset of embryonic differentiation in developing oocytes, which is required to ensure a successful transition between generations.
2014-01-01 | S-EPMC4148191 | BioStudies
Project description:Establishment and maintenance of proper gene expression is a requirement for normal growth and development. The DREAM complex in Caenorhabditis elegans functions as a transcriptional repressor of germline genes in somatic cells. At 26°, DREAM complex mutants show increased misexpression of germline genes in somatic cells and High Temperature Arrest (HTA) of worms at the first larval stage. To identify transcription factors required for the ectopic expression of germline genes in DREAM complex mutants, we conducted an RNA interference screen against 123 transcription factors capable of binding DREAM target promoter loci for suppression of the HTA phenotype in lin-54 mutants. We found that knock-down of 15 embryonically expressed transcription factors suppress the HTA phenotype in lin-54 mutants. Five of the transcription factors found in the initial screen have associations with Wnt signaling pathways. In a subsequent RNAi suppression screen of Wnt signaling factors we found that knock-down of the non-canonical Wnt/PCP pathway factors vang-1, prkl-1 and fmi-1 in a lin-54 mutant background resulted in strong suppression of the HTA phenotype. Animals mutant for both lin-54 and vang-1 showed almost complete suppression of the HTA phenotype, pgl-1 misexpression, and fertility defects associated with lin-54 single mutants at 26°. We propose a model whereby a set of embryonically expressed transcription factors, and the Wnt/PCP pathway, act opportunistically to activate DREAM complex target genes in somatic cells of DREAM complex mutants at 26°.
2020-01-01 | S-EPMC7003081 | BioStudies
Project description:DRM is a conserved transcription factor complex that includes E2F/DP and pRB family proteins and plays important roles in development and cancer. Here we analyze genome-wide binding and function of the C. elegans DRM subunit LIN-54. We demonstrate that LIN-54 DNA-binding activity is required for the DRM complex to efficiently bind and regulate target genes containing adjacent putative E2F/DP and LIN-54 binding sites. We show that LIN-54 binds to the promoters of genes involved in cell division, development, and reproduction, and acts differently in the germline versus the soma. The E2F/DP-LIN-54 binding motif, individual target genes, and overall DRM function are conserved among worms, flies, and humans. Despite this conservation, we discovered one striking feature of C. elegans DRM not shared in flies or humans: it is depleted from X chromosomes. We show that DRM binding, the E2F-LIN-54 hybrid motif, and LIN-54-regulated genes are all autosome-enriched. Chromatin-immunoprecipitation of mixed staged wild-type C.elegans (N2, Bristol strain) was performed using non-commercial anti-LIN-54 antibody raised in guinea pig (Harrison et at. 2006).
2011-04-27 | E-GEOD-28852 | ArrayExpress
Project description:The Retinoblastoma-like pocket proteins p130 and p107 act as gatekeepers of the cell cycle through their activity within the DREAM (Dp/Rb-like/E2F/MuvB) transcriptional repressor complex. The goal of this study was to address how the pocket protein contributes to DREAM complex assembly and function on chromatin by utilizing a protein null mutant of the only C. elegans pocket protein LIN-35. We performed ChIP-seq of C. elegans DRM subunits in wild-type and lin-35 null late embryos to assess the effect on their chromatin localization following loss of LIN-35. Overall design: Examination of 7 DRM complex subunits (DPL-1, EFL-1, LIN-35, LIN-9, LIN-37, LIN-52, and LIN-54) in lin-35(n745) (a protein null strain) and WT C. elegans late stage embryos to assess effects of loss of LIN-35 on DRM complex chromatin assembly. Study includes reanalysis of GSM1195397 and GSM1195398 (GSE49204) with an additional replicate, generating the following processed data: LIN-37.SDQ3166.N2.rep0.vsInputRep0.SES.bw LIN-37.SDQ3166.N2.IDR.0.01.narrowPeak
2017-10-25 | GSE95071 | GEO