title: HES-Mediated Repression of Pten in Caenorhabditis elegans.
abstract: The hairy/enhancer-of-split (HES) group of transcription factors controls embryonic development, often by acting downstream of the Notch signaling pathway; however, little is known about postembryonic roles of these proteins. In Caenorhabditis elegans, the six proteins that make up the REF-1 family are considered to be HES orthologs that act in both Notch-dependent and Notch-independent pathways to regulate embryonic events. To further our understanding of how the REF-1 family works to coordinate postembryonic cellular events, we performed a functional characterization of the REF-1 family member, HLH-25. We show that, after embryogenesis, hlh-25 expression persists throughout every developmental stage, including dauer, into adulthood. Like animals that carry loss-of-function alleles in genes required for normal cell-cycle progression, the phenotypes of hlh-25 animals include reduced brood size, unfertilized oocytes, and abnormal gonad morphology. Using gene expression microarray, we show that the HLH-25 transcriptional network correlates with the phenotypes of hlh-25 animals and that the C. elegans Pten ortholog, daf-18, is one major hub in the network. Finally, we show that HLH-25 regulates C. elegans lifespan and dauer recovery, which correlates with a role in the transcriptional repression of daf-18 activity. Collectively, these data provide the first genetic evidence that HLH-25 may be a functional ortholog of mammalian HES1, which represses PTEN activity in mice and human cells.
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303 Center for Obesity Reversal, Georgia State University, Atlanta, Georgia 30303.
authors.forename: Han Ting
authors.identifier: http://orcid.org/0000-0002-1259-2694
authors.initials: HT
authors.lastname: Chou
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303.
authors.forename: Raymarie Gomez
authors.initials: RG
authors.lastname: Vazquez
authors.affiliation: Department of Environmental Health Science, Division of Biostatistics, New York University School of Medicine, New York, New York 10016.
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303.
authors.forename: Richard
authors.initials: R
authors.lastname: Campbell
authors.affiliation: Department of Mathematics and Computer Science, North Carolina Central University, Durham, North Carolina 27707.
authors.forename: Gaolin Zheng
authors.initials: GZ
authors.lastname: Milledge
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303.
authors.forename: Walter W
authors.initials: WW
authors.lastname: Walthall
authors.affiliation: Department of Biology, Georgia State University, Atlanta, Georgia 30303 Center for Obesity Reversal, Georgia State University, Atlanta, Georgia 30303 cjohnson113@gsu.edu.
authors.forename: Casonya M
authors.initials: CM
authors.lastname: Johnson
mesh_terms: D000483:Alleles; D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism*; D047108:Embryonic Development / Q000235:genetics; D005260:Female; D018507:Gene Expression Regulation, Developmental; D053263:Gene Regulatory Networks; D006066:Gonads / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009865:Oocytes / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010641:Phenotype; D015203:Reproducibility of Results; D012098:Reproduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D014157:Transcription Factors; D051059:PTEN Phosphohydrolase
keywords: dauer recovery; gene expression microarray; gonad morphology; hairy/enhancer-of-split; unfertilized oocytes