title: The GATA factor elt-1 regulates C. elegans developmental timing by promoting expression of the let-7 family microRNAs.
abstract: Postembryonic development in Caenorhabditis elegans is a powerful model for the study of the temporal regulation of development and for the roles of microRNAs in controlling gene expression. Stable switch-like changes in gene expression occur during development as stage-specific microRNAs are expressed and subsequently down-regulate other stage-specific factors, driving developmental progression. Key genes in this regulatory network are phylogenetically conserved and include the post-transcriptional microRNA repressor LIN-28; the nuclear hormone receptor DAF-12; and the microRNAs LIN-4, LET-7, and the three LET-7 family miRNAs (miR-48, miR-84, and miR-241). DAF-12 is known to regulate transcription of miR-48, miR-84 and miR-241, but its contribution is insufficient to account for all of the transcriptional regulation implied by the mutant phenotypes. In this work, the GATA-family transcription factor ELT-1 is identified from a genetic enhancer screen as a regulator of developmental timing in parallel to DAF-12, and is shown to do so by promoting the expression of the LET-7, miR-48, miR-84, and miR-241 microRNAs. The role of ELT-1 in developmental timing is shown to be separate from its role in cell-fate maintenance during post-embryonic development. In addition, analysis of Chromatin Immnoprecipitation (ChIP) data from the modENCODE project and this work suggest that the contribution of ELT-1 to the control of let-7 family microRNA expression is likely through direct transcription regulation.
authors: Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America.
authors: Max L
authors: ML
authors: Cohen
authors: Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America; Incurable Disease Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea.
authors: Sunhong
authors: S
authors: Kim
authors: Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America.
authors: Kiyokazu
authors: K
authors: Morita
authors: Incurable Disease Therapeutics Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongju, Republic of Korea; Department of Biomolecular Science, University of Science and Technology, Daejeon, Republic of Korea.
authors: Seong Heon
authors: SH
authors: Kim
authors: Howard Hughes Medical Institute and Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder, Colorado, United States of America.
authors: Min
authors: M
authors: Han
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development; D029742:Caenorhabditis elegans Proteins / Q000096:biosynthesis* / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D050980:GATA Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C410905:DAF-12 protein, C elegans; C096869:ELT-1 protein, C elegans; D050980:GATA Transcription Factors; D035683:MicroRNAs; D018160:Receptors, Cytoplasmic and Nuclear; C474488:let-7 microRNA, C elegans