RRC ID 53443
Author Wiesenfahrt T, Berg JY, Osborne Nishimura E, Robinson AG, Goszczynski B, Lieb JD, McGhee JD.
Title The function and regulation of the GATA factor ELT-2 in the C. elegans endoderm.
Journal Development
Abstract ELT-2 is the major regulator of genes involved in differentiation, maintenance and function of C. elegans intestine from the early embryo to mature adult. elt-2 responds to overexpression of the GATA transcription factors END-1 and END-3, which specify the intestine, as well as to overexpression of the two GATA factors that are normally involved in intestinal differentiation, ELT-7 and ELT-2 itself. Little is known about the molecular mechanisms underlying these interactions, how ELT-2 levels are maintained throughout development or how such systems respond to developmental perturbations. Here, we analyse elt-2 gene regulation through transgenic reporter assays, ELT-2 ChIP and characterisation of in vitro DNA-protein interactions. Our results indicate that elt-2 is controlled by three discrete regulatory regions conserved between C. elegans and C. briggsae that span >4 kb of 5' flanking sequence. These regions are superficially interchangeable but have quantitatively different enhancer properties, and their combined activities indicate inter-region synergies. Their regulatory activity is mediated by a small number of conserved TGATAA sites that are largely interchangeable and interact with different endodermal GATA factors with only modest differences in affinity. The redundant molecular mechanism that forms the elt-2 regulatory network is robust and flexible, as loss of end-3 halves ELT-2 levels in the early embryo but levels fully recover by the time of hatching. When ELT-2 is expressed under the control of end-1 regulatory elements, in addition to its own endogenous promoter, it can replace the complete set of endoderm-specific GATA factors: END-1, END-3, ELT-7 and (the probably non-functional) ELT-4. Thus, in addition to controlling gene expression during differentiation, ELT-2 is capable of specifying the entire C. elegans endoderm.
Volume 143(3)
Pages 483-91
Published 2016-2-1
DOI 10.1242/dev.130914
PII dev.130914
PMID 26700680
PMC PMC4760314
MeSH 5' Flanking Region / genetics Animals Base Sequence Caenorhabditis elegans / embryology* Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Cell Differentiation / genetics Chromatin Immunoprecipitation Conserved Sequence DNA / metabolism Endoderm / embryology* Endoderm / metabolism* GATA Transcription Factors / genetics* GATA Transcription Factors / metabolism Gene Expression Regulation, Developmental* Gene Regulatory Networks Intestinal Mucosa / metabolism Molecular Sequence Data Promoter Regions, Genetic Protein Binding / genetics Transcription Factors / metabolism Transcription, Genetic
IF 5.763
Times Cited 13
C.elegans tm840