Regulation of chromatin states and gene expression during HSN neuronal maturation is mediated by EOR-1/PLZF, MAU-2/cohesin loader, and SWI/SNF complex

Abstract

Newborn neurons mature by distinct and sequential steps through the timely induction of specific gene expression programs in concert with epigenetic changes. However, it has been difficult to investigate the relationship between gene expression and epigenetic changes at a single-cell resolution during neuronal maturation. In this study, we investigated the maturation of hermaphrodite-specific neurons (HSNs) in C. elegans, which provided the link between chromatin dynamics, gene expression, and the degree of neuronal maturation at a single-cell resolution. Our results demonstrated that chromatin composition in the promoter region of several genes acting for neuronal terminal maturation was modulated at an early developmental stage, and is dependent on the function of the transcription factor EOR-1/PLZF and the cohesin loader MAU-2/MAU2. Components of the SWI/SNF chromatin remodeling complex were also required for the proper expression of terminal maturation genes. Epistasis analyses suggested that eor-1 functions with mau-2 and swsn-1 in the same genetic pathway to regulate the maturation of HSNs. Collectively, our study provides a novel approach to analyze neuronal maturation and proposes that predefined epigenetic modifications, mediated by EOR-1, MAU-2, and the SWI/SNF complex, are important for the preparation of future gene expression programs in neuronal terminal maturation.

H3K9me selectively blocks transcription factor activity and ensures differentiated tissue integrity

“…At the genes that gain both accessibility and expression (Group B), an analysis of TF motifs indicated that chromatin decompaction may well be a secondary effect of TF binding, as the TFs recruit additional complexes that in turn regulate chromatin opening. Notably, the bZIP TFs that co-map with Group B loci as well as Onecut1/2, the CEH-48 homologue, recruit the CBP/p300 histone acetyltransferase, and EOR-1 cooperates with the SWI/SNF chromatin remodeler 51 , 54 – 57 . Thus, depending on the chromatin factors that are recruited, different TFs may trigger different degrees of chromatin opening (Fig.…”

“…In the non-derepressed Group C, which nonetheless gained ATAC-seq sensitivity, the only motifs significantly enriched were for EOR-1, DAF-12/NHR-48 and ZTF-3. Importantly, all three of these factors have been shown to bind enhancers during C. elegans development 47 , 51 .…”