title: The Caenorhabditis elegans GATA factor ELT-1 works through the cell proliferation regulator BRO-1 and the Fusogen EFF-1 to maintain the seam stem-like fate.
abstract: Seam cells in Caenorhabditis elegans provide a paradigm for the stem cell mode of division, with the ability to both self-renew and produce daughters that differentiate. The transcription factor RNT-1 and its DNA binding partner BRO-1 (homologues of the mammalian cancer-associated stem cell regulators RUNX and CBFβ, respectively) are known rate-limiting regulators of seam cell proliferation. Here, we show, using a combination of comparative genomics and DNA binding assays, that bro-1 expression is directly regulated by the GATA factor ELT-1. elt-1(RNAi) animals display similar seam cell lineage defects to bro-1 mutants, but have an additional phenotype in which seam cells lose their stem cell-like properties and differentiate inappropriately by fusing with the hyp7 epidermal syncytium. This phenotype is dependent on the fusogen EFF-1, which we show is repressed by ELT-1 in seam cells. Overall, our data suggest that ELT-1 has dual roles in the stem-like seam cells, acting both to promote proliferation and prevent differentiation.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford, United Kingdom.
authors.forename: Charles
authors.initials: C
authors.lastname: Brabin
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Appleford
authors.forename: Alison
authors.initials: A
authors.lastname: Woollard
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000235:genetics; D002455:Cell Division / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D007365:Intercellular Junctions / Q000378:metabolism; D007438:Introns / Q000235:genetics; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D040521:Subcutaneous Tissue / Q000378:metabolism
chemical_list: C525389:BRO-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; C470734:EFF-1 protein, C elegans; C096869:ELT-1 protein, C elegans; D050980:GATA Transcription Factors; D008562:Membrane Glycoproteins; D012097:Repressor Proteins