GSE96908
Genome-wide Analysis of Binding Sites of the Caenorhabditis elegans NR4A Nuclear Receptor NHR-6 During Spermatheca Organogenesis
The gene nhr-6 encodes the sole C. elegans NR4A nuclear receptor homolog which has a critical role in organogenesis by regulating the development of the spermatheca organ. Here we utilized chromatin immunoprecipitation followed by next-generation sequencing (ChIP-seq) to identify NHR-6 binding sites during both the late L3/early L4 and mid L4 developmental stages. Our results revealed 30,745 enriched binding sites for NHR-6 with sites specific to each developmental stage and sites found in both stages. Additionally, ~70% of enriched sites were found within 3 kb upstream of a gene transcription start site. Binding sites for a cohort of candidate target genes with probable functions in spermatheca organogenesis were validated through qPCR. Reproductive and spermatheca phenotypes were also evaluated for these genes following a loss-of-function RNAi screen which revealed several genes with critical functions during spermatheca organogenesis. Our results uncovered a complex nuclear receptor regulatory network whereby NHR-6 regulates multiple cellular processes including proliferation, differentiation, and metabolism. Overall design: Identification of NHR-6 binding sites using ChIP-seq at two developmental stages