Binding Site Analysis of the Caenorhabditis elegans NR4A Nuclear Receptor NHR-6 During Development
| Autor: | Vittobai Rashika Rangaraj, Jeremy S. Harmson, Joohyun Kim, Chris R. Gissendanner, Brandon Praslicka, Aikseng Ooi |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Genetics Cellular differentiation Organogenesis General Medicine Biology biology.organism_classification NR4A Article ChIP-seq lcsh:Biochemistry 03 medical and health sciences 030104 developmental biology spermatheca Nuclear receptor Spermatheca nhr-6 lcsh:Q lcsh:QD415-436 Caenorhabditis elegans lcsh:Science Gene Transcription factor Chromatin immunoprecipitation |
| Zdroj: | Nuclear Receptor Research, Vol 4, Pp 1-17 (2017) |
| ISSN: | 2314-5714 |
| Popis: | Members of the NR4A subfamily of nuclear receptors make up a highly conserved, functionally diverse group of transcription factors implicated in a multitude of cellular processes such as proliferation, differentiation, apoptosis, metabolism and DNA repair. The gene nhr-6, which encodes the sole C. elegans NR4A nuclear receptor homolog, has a critical role in organogenesis and regulates the development of the spermatheca organ system. Our previous work revealed that nhr-6 is required for spermatheca cell divisions in late L3 and early L4 and spermatheca cell differentiation during the mid L4 stage. 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, ~70% of which were 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 during spermatheca organogenesis. |
| Databáze: | OpenAIRE |
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