title: Identification of cis-regulatory elements from the C. elegans Hox gene lin-39 required for embryonic expression and for regulation by the transcription factors LIN-1, LIN-31 and LIN-39.
abstract: Expression of the Caenorhabditis elegans Hox gene lin-39 begins in the embryo and continues in multiple larval cells, including the P cell lineages that generate ventral cord neurons (VCNs) and vulval precursor cells (VPCs). lin-39 is regulated by several factors and by Wnt and Ras signaling pathways; however, no cis-acting sites mediating lin-39 regulation have been identified. Here, we describe three elements controlling lin-39 expression: a 338-bp upstream fragment that directs embryonic expression in P5-P8 and their descendants in the larva, a 247-bp intronic region sufficient for VCN expression, and a 1.3-kb upstream cis-regulatory module that drives expression in the VPC P6.p in a Ras-dependent manner. Three trans-acting factors regulate expression via the 1.3-kb element. A single binding site for the ETS factor LIN-1 mediates repression in VPCs other than P6.p; however, loss of LIN-1 decreases expression in P6.p. Therefore, LIN-1 acts both negatively and positively on lin-39 in different VPCs. The Forkhead domain protein LIN-31 also acts positively on lin-39 in P6.p via this module. Finally, LIN-39 itself binds to this element, suggesting that LIN-39 autoregulates its expression in P6.p. Therefore, we have begun to unravel the cis-acting sites regulating lin-39 Hox gene expression and have shown that lin-39 is a direct target of the Ras pathway acting via LIN-1 and LIN-31.
authors.affiliation: Department of Biological Sciences, University of Maryland Baltimore County, Baltimore, MD 21250, USA.
authors.forename: Javier A
authors.initials: JA
authors.lastname: Wagmaister
authors.forename: Ginger R
authors.initials: GR
authors.lastname: Miley
authors.forename: Corey A
authors.initials: CA
authors.lastname: Morris
authors.forename: Julie E
authors.initials: JE
authors.lastname: Gleason
authors.forename: Leilani M
authors.initials: LM
authors.lastname: Miller
authors.forename: Kerry
authors.initials: K
authors.lastname: Kornfeld
authors.forename: David M
authors.initials: DM
authors.lastname: Eisenmann
mesh_terms: D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism / Q000502:physiology; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C097533:Lin-1 protein, C elegans; D014157:Transcription Factors; C081464:lin-31 protein, C elegans; C108673:lin-39 protein, C elegans