title: Genome-wide microarrray analysis reveals roles for the REF-1 family member HLH-29 in ferritin synthesis and peroxide stress response.
abstract: In Caenorhabditis elegans, the six proteins that make up the REF-1 family have been identified as functional homologs of the Hairy/Enhancer of Split (HES) proteins. These transcription factors act in both Notch dependent and Notch-independent pathways to regulate embryonic events during development; however, their post-embryonic functions are not well defined. As a first step toward understanding how the REF-1 family works together to coordinate post-embryonic events, we used gene expression microarray analysis to identify transcriptional targets of HLH-29 in L4/young adult stage animals. Here we show that HLH-29 targets are genes needed for the regulation of growth and lifespan, including genes required for oxidative stress response and fatty acid metabolism, and the ferritin genes, ftn-1 and ftn-2. We show that HLH-29 regulates ftn-1 expression via promoter sequences upstream of the iron-dependent element that is recognized by the hypoxia inducible factor, HIF-1. Additionally, hlh-29 mutants are more resistant to peroxide stress than wild-type animals and ftn-1(RNAi) animals, even in the presence of excess iron. Finally we show that HLH-29 acts parallel to DAF-16 but upstream of the microphthalmia transcription factor ortholog, HLH-30, to regulate ftn-1 expression under normal growth conditions.
authors.affiliation: Department of Biology, College of Arts and Sciences, Georgia State University, Atlanta, Georgia, United States of America.
authors.forename: Thanh K
authors.initials: TK
authors.lastname: Quach
authors.forename: Han Ting
authors.initials: HT
authors.lastname: Chou
authors.forename: Kun
authors.initials: K
authors.lastname: Wang
authors.forename: Gaolin Zheng
authors.initials: GZ
authors.lastname: Milledge
authors.forename: Casonya M
authors.initials: CM
authors.lastname: Johnson
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D005293:Ferritins / Q000096:biosynthesis*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007501:Iron / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D025341:Principal Component Analysis
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D029742:Caenorhabditis elegans Proteins; D005293:Ferritins; D006861:Hydrogen Peroxide; D007501:Iron; C518216:HLH-29 protein, C elegans; C428453:ref-1 protein, C elegans