TRA-1A regulates transcription of fog-3, which controls germ cell fate in C. elegans

Abstract

In C. elegans, the zinc-finger protein TRA-1A is thought to be the final arbiter of somatic sexual identity. We show that fog-3, which is required for germ cells to become sperm rather than oocytes, is a target of TRA-1A. First, northern analyses and RT-PCR experiments indicate that expression of fog-3 is controlled by tra-1. Second, studies of double mutants show that this control could be direct. Third, the fog-3 promoter contains multiple sites that bind TRA-1A in gel shift assays, and mutations in these sites alter activity of fog-3 in vivo. These results establish fog-3 as one of the first known targets of transcriptional regulation by TRA-1A. Furthermore, they show that tra-1 controls a terminal regulator of sexual fate in germ cells, just as it is thought to do in the soma.

The TRA-1 transcription factor binds TRA-2 to regulate sexual fates in Caenorhabditis elegans

“…The fog‐3 gene is required for specification of sperm (Ellis and Kimble, 1995), and harbors a series of TRA‐1 binding sites in its promoter (Chen and Ellis, 2000). Intriguingly, these TRA‐1 sites can mediate either repression or activation of the fog‐3 promoter (Chen and Ellis, 2000). One simple idea is that TRA‐1 activates fog‐3 at one level of expression or in one state which exists in males and larval hermaphrodites as sperm are specified, and represses fog‐3 at a second level or state which exists during oogenesis.…”

“…One mechanism by which TRA‐1 controls germ‐line sexual fates appears to be transcriptional. The fog‐3 gene is required for specification of sperm (Ellis and Kimble, 1995), and harbors a series of TRA‐1 binding sites in its promoter (Chen and Ellis, 2000). Intriguingly, these TRA‐1 sites can mediate either repression or activation of the fog‐3 promoter (Chen and Ellis, 2000).…”

“…Conservation of the TRA-1±TRA-2 interaction The tra-1 and tra-2 genes are among the most divergent genes in C.elegans and C.briggsae (de Bono and Hodgkin, 1996;Kuwabara, 1996). Each C.elegans protein is only ~40% identical to its C.briggsae homolog.…”

“…The C.briggsae tra-1 and tra-2 genes are functionally similar to their C.elegans relatives (Kuwabara and Shah, 1994;de Bono and Hodgkin, 1996) and the MX region is conserved (Kuwabara and Shah, 1994) (Figure 7A). If the TRA-1±TRA-2 interaction is critical for sex determination, that interaction should also be conserved.…”

Sexual dimorphism in Caenorhabditis elegans stress resistance

“…TRA-1 is a transcriptional repressor and was found to bind to at least 184 genes with ChIP-seq making identification of downstream mechanisms potentially complicated [90]. However, genetic analyses have identified some key downstream regulators of sexual characteristics that could be tested for effects on stress resistance [91][92][93][94]; these include mab-3 (Male Abnormal), dmd-3 (Doublesex/Mab-3 Domain), ceh-30 (C. Elegans Homeobox), egl-1 (EGg Laying defective), fog-1 (Feminization Of Germline), and fog-3; MAB-3 represses vitellogenin genes needed to provide yoke to oocytes [95][96][97], MAB-3 and DMD-3 control male-tail development [98], CEH-30 and EGL-1 protect male-specific neurons from undergoing apoptosis [91], and FOG-1 and FOG-3 regulate sexual characteristics of the germline [93,94]. Mutations in these pathways feminize or masculinize these specific processes and, in future studies, can be tested for effects on stress resistance.…”