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.

Diverse transcription factor binding features revealed by genome-wide ChIP-seq in C. elegans

“…The resulting network shows a surprisingly large number of potential regulatory interactions. Consistent with previous studies, we can detect an autoregulatory relationship for TFs containing a HOX domain such as LIN-39 (Wagmaister et al 2006). Additionally, we found that ALR-1 binds to the lin-39 regulatory region, which is consistent with data from a yeast one-hybrid interaction assay (W. Liu and D. Eisenmann, pers.…”

Differentiation of Carbon Dioxide-Sensing Neurons in Caenorhabditis elegans Requires the ETS-5 Transcription Factor

“…The binding sites for mammalian ETS proteins are well characterized, and at least some of the C. elegans ETS proteins bind to cis-regulatory motifs that are similar to mammalian ETS binding sites (Wagmaister et al 2006;Flames and Hobert 2009;Thyagarajan et al 2010). All mammalian ETS family members bind to the conserved core recognition sequence 59-GGA(A/T)-39, and the bases surrounding this core recognition sequence determine binding specificity for individual ETS proteins (Macleod et al 1992;Hollenhorst et al 2011).…”

TheC. elegansSoxC protein SEM-2 opposes differentiation factors to promote a proliferative blast cell fate in the postembryonic mesoderm

“…Both mab-5 and ceh-20 are expressed throughout the M lineage (Liu and Fire, 2000;Jiang et al, 2009), whereas lin-39 is expressed in the SM lineage (Wagmaister et al, 2006). Furthermore, MAB-5 and LIN-39 together, and CEH-20 are required for the proper specification and differentiation of Mderived CC, BWMs and SMs (Jiang et al, 2009).…”

“…5B,C). However, these three genes are also expressed in other cell types in C. elegans (Costa et al, 1988;Wagmaister et al, 2006;Jiang et al, 2009). In fact, it has been shown that MAB-5/CEH-20 and/or LIN-39/CEH-20 complexes directly activate the expression of hlh-8 throughout the M lineage before terminal differentiation (Liu and Fire, 2000), of egl-18, elt-6, eff-1 and lag-2 in the developing vulva (Koh et al, 2002;Shemer and Podbilewicz, 2002;Takacs-Vellai et al, 2007), and of egl-1 in the P11 lineage and the VC neurons Potts et al, 2009).…”