Dataset Information

Effect of loss-of-function of ZFP-1, DOT-1.1 and MML-1 on gene expression in C. elegans

ABSTRACT: Transcriptional control is mediated by interactions of transcription factors with their cognate DNA elements, as well as by epigenetic modifications to chromatin catalyzed by a variety of enzymes. Thus, understanding the crosstalk between transcription factors and epigenetic modifiers is of prime importance. The Dot1-like protein (DOT1L) is an evolutionary conserved methyltransferase with catalytic specificity towards histone 3 lysine 79 (H3K79). DOT1L is essential for mammalian development and has been studied mostly in the context of aggressive leukemias. Recent observations suggest that the role of DOT1L in malignant transformation can be generalized to contexts beyond leukemia. For instance, DOT1L has been implicated in breast cancer progression, and this has been attributed to its cooperation with c-Myc. However, the mechanistic details underlying this association are unknown. Previous work in our lab has shown that DOT-1.1, the C. elegans DOT1L homologue, is recruited to chromatin by ZFP-1 (similarly to DOT1L recruitment by AF10 in mammals), and this complex negatively modulates transcription. Interestingly, promoters of ZFP-1/DOT-1.1 target genes are enriched in E-boxes, the consensus binding motif for c-Myc. Prompted by the exciting hypothesis that DOT-1.1 and MML-1, the C. elegans c-Myc homologue, cooperate genome-wide, we profiled gene expression in wild-type worms and dot-1.1(gk105059), zfp-1(ok554), and mml-1(gk402844) loss-of-function mutants by microarray. We found significant overlaps between genes upregulated in the three mutants, and the same was observed for downregulated genes. A significant global increase of non-coding transcripts was observed in either mutant compared with wild-type. Therefore, ZFP-1/DOT-1.1 and MML-1 co-regulate both coding and non-coding genes and globally inhibit non-coding transcription. Further investigation is underway to uncover the mechanism of cooperation of ZFP-1/DOT-1.1 and MML-1. Profiling of gene expression in wild-type third larval stage (L3) larvae and zfp-1(ok554), dot-1.1(gk105059) and mml-1(gk402844) mutant worms.

ORGANISM(S): Caenorhabditis elegans

PROVIDER: GSE115677 | GEO | 2021/09/09

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:modENCODE_submission_2943 This submission comes from a modENCODE project of Michael Snyder. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We are identifying the DNA binding sites for 300 transcription factors in C. elegans. Each transcription factor gene is tagged with the same GFP fusion protein, permitting validation of the gene's correct spatio-temporal expression pattern in transgenic animals. Chromatin immunoprecipitation on each strain is peformed using an anti-GFP antibody, and any bound DNA is deep-sequenced using Solexa GA2 technology. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-seq. BIOLOGICAL SOURCE: Strain: OP198(official name : OP198 genotype : unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The MML-1::EGFP fusion protein is expressed in the correct mml-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the MML-1 transcription factor. made_by : R Waterston ); Developmental Stage: L3; Genotype: unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119); Sex: Hermaphrodite; EXPERIMENTAL FACTORS: Developmental Stage L3; Target gene mml-1; Strain OP198(official name : OP198 genotype : unc-119(ed3); wgIs198(mml-1::TY1 EGFP FLAG C; unc-119) outcross : 3 mutagen : Bombard tags : GFP::3xFlag description : This strain's transgene was constructed by Mihail Sarov at the Max Planck Institute for Cell Biology in Tubiginen using Tony Hyman's recombineering pipeline. The resulting plasmid was used for biolistic transformation of an unc-119(ed3) strain. The MML-1::EGFP fusion protein is expressed in the correct mml-1 spatio-temporal expression pattern. This strain was used for ChIP-seq experiments to map the in vivo binding sites for the MML-1 transcription factor. made_by : R Waterston ); temp (temperature) 20 degree celsius

Dataset Information

Effect of loss-of-function of ZFP-1, DOT-1.1 and MML-1 on gene expression in C. elegans

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure