Caenorhabditis elegans SWI/SNF Subunits Control Sequential Developmental Stages in the Somatic Gonad

Abstract

The Caenorhabditis elegans somatic gonadal precursors (SGPs) are multipotent progenitors that give rise to all somatic tissues of the adult reproductive system. The hunchback and Ikaros-like gene ehn-3 is expressed specifically in SGPs and is required for their development into differentiated tissues of the somatic gonad. To find novel genes involved in SGP development, we used a weak allele of ehn-3 as the basis for a reverse genetic screen. Feeding RNAi was used to screen ∼2400 clones consisting of transcription factors, signaling components, and chromatin factors. The screen identified five members of the C. elegans SWI/SNF chromatin remodeling complex as genetic enhancers of ehn-3. We characterized alleles of 10 SWI/SNF genes and found that SWI/SNF subunits are required for viability and gonadogenesis. Two conserved SWI/SNF complexes, PBAF and BAF, are defined by their unique array of accessory subunits around a common enzymatic core that includes a catalytic Swi2/Snf2–type ATPase. Tissue-specific RNAi experiments suggest that C. elegans PBAF and BAF complexes control different processes during somatic gonadal development: PBRM-1, a signature subunit of PBAF, is important for normal SGP development, whereas LET-526, the distinguishing subunit of BAF, is required for development of a differentiated cell type, the distal tip cell (DTC). We found that the SWSN-4 ATPase subunit is required for SGP and DTC development. Finally, we provide evidence that C. elegans PBAF subunits and hnd-1/dHand are important for the cell fate decision between SGPs and their differentiated sisters, the head mesodermal cells.

SWI/SNF chromatin remodeling regulates alcohol response behaviors in Caenorhabditis elegans and is associated with alcohol dependence in humans

“…Thirteen C. elegans SWI/SNF genes have been characterized to date, and they include homologs of all major human SWI/SNF subunits (26)(27)(28)(29)(30)(31). Mammalian SWI/SNF complexes have been biochemically purified from different tissues and found to contain unique combinations of subunits depending upon cell type and developmental stage (32).…”

“…The complexes classically have been grouped into the Brg1-associated factors (BAF) and polybromo-associated BAF (PBAF) subfamilies based on the incorporation of complex-specific subunits (33, reviewed in 34). These distinctions are likely to extend to C. elegans, because mutations affecting BAF-and PBAF-specific subunits have distinct phenotypes in worms (26,29).…”

“…First, swsn-3(tm3647) was the only SWI/SNF mutant that was hypersensitive to ethanol. This mutation is unusual in that it is predicted to produce a truncated SWSN-3 protein lacking the HMG domain (26) and therefore may produce a gain-of-function phenotype. Second, the pbrm-1 (ok843) mutant was resistant to ethanol, and it developed AFT.…”

“…The SWI/SNF complex is important for embryonic and larval development (26,(28)(29)(30)(31); therefore SWI/SNF may be required during development and/or in adulthood for AFT. To distinguish between these possibilities, we took advantage of a temperaturesensitive allele of swsn-1 (28).…”

Functional Interplay of Two Paralogs Encoding SWI/SNF Chromatin-Remodeling Accessory Subunits DuringCaenorhabditis elegansDevelopment

“…In addition to these common functions, ham-3 has been described to be involved in neuronal specification and in the transcriptional regulation of specific microRNAs (Hayes et al 2011;Weinberg et al 2013). Differently from ham-3, loss of swsn-2.2 produces Emb (embryonic lethality) and Psa (phasmid socket absent; specific cells acquiring hypodermal fate instead of the neuronal fate) phenotypes at high penetrance (Sawa et al 2000;Large and Mathies 2014).Although ham-3 and swsn-2.2 have been associated with various developmental mechanisms, the functional interplay of the two proteins in different stages and tissues has not been formally studied. We have compiled mutant alleles for the two genes and isolated he159, a new allele for ham-3.…”