Chromatin dynamics enable transcriptional rhythms in the cnidarian Nematostella vectensis

Abstract

In animals, circadian rhythms are driven by oscillations in transcription, translation, and proteasomal degradation of highly conserved genes, resulting in diel cycles in the expression of numerous clock-regulated genes. Transcription is largely regulated through the binding of transcription factors to cis-regulatory elements within accessible regions of the chromatin. Chromatin remodeling is linked to circadian regulation in mammals, but it is unknown whether cycles in chromatin accessibility are a general feature of clock-regulated genes throughout evolution. To assess this, we applied an ATAC-seq approach using Nematostella vectensis, grown under two separate light regimes (light:dark (LD) and constant darkness (DD)). Based on previously identified N. vectensis circadian genes, our results show the coupling of chromatin accessibility and circadian transcription rhythmicity under LD conditions. Out of 180 known circadian genes, we were able to list 139 gene promoters that were highly accessible compared to common promoters. Furthermore, under LD conditions, we identified 259 active enhancers as opposed to 333 active enhancers under DD conditions, with 171 enhancers shared between the two treatments. The development of a highly reproducible ATAC-seq protocol integrated with published RNA-seq and ChIP-seq databases revealed the enrichment of transcription factor binding sites (such as C/EBP, homeobox, and MYB), which have not been previously associated with circadian signaling in cnidarians. These results provide new insight into the regulation of cnidarian circadian machinery. Broadly speaking, this supports the notion that the association between chromatin remodeling and circadian regulation arose early in animal evolution as reflected in this non-bilaterian lineage.

Epigenomic landscape of enhancer elements during Hydra head organizer formation

“…Owing to this, their divergence at the base of metazoans, where major evolutionary transitions took place with respect to developmental processes such as axis pattering and cell type functions, is poorly understood. Until now very few studies have reported the identification of the enhancer elements from the basal metazoan phylum Cnidaria suggesting their roles in gene regulation in different paradigms [ 31 , 50 , 51 ].…”

Chromatin Dynamics and Gene Expression Response to Heat Exposure in Field-Conditioned versus Laboratory-Cultured Nematostella vectensis

“…Yet, there is little knowledge about the relationship between promoter accessibility and its related gene expression, as various regulatory mechanisms can regulate cnidarian gene activity. For example, we have previously shown that clock-controlled genes present different accessibility patterns over a 24 h period [ 22 ]. It was found that promoters of some clock-controlled genes were constantly accessible, whereas the accessibility of others oscillated [ 22 ].…”

“…For example, we have previously shown that clock-controlled genes present different accessibility patterns over a 24 h period [ 22 ]. It was found that promoters of some clock-controlled genes were constantly accessible, whereas the accessibility of others oscillated [ 22 ]. Further research is needed in the field of epigenetics and, more specifically, on chromatin spatial interactions, in order to elucidate how promoter accessibility is linked with changes in gene expression in cnidarians.…”

Epigenetic Regulation in Hydra: Conserved and Divergent Roles

“…ATAC-seq mapping in neurons of the cnidarian N. vectensis revealed neuron-specific gene accessibility patterns that correlated with neuronal transcription profiles ( Sebé-Pedrós et al, 2018 ). A positive correlation between gene accessibility and transcription has been observed for most circadian rhythm-regulated gene promoters in the starlet sea anemone N. vectensis , which also has distal regions with enhancer-like properties, and thermal stress-responsive genes in the coral Aiptasia pallida ( Weizman and Levy, 2019 ; Weizman et al, 2019 ). In a recent study, Reddy et al (2020b) showed that unlike in higher metazoans, RNA Pol II does not pause at the TSSs of most genes in H. vulgaris Ind-Pune and is instead uniformly distributed across gene bodies, with its occupancy positively correlated with the expression level.…”

“…This study indicated that bilaterian enhancer characters are conserved in N. vectensis ( Schwaiger et al, 2014 ). Among these, ∼600 enhancers have been shown to play a role in transcription regulation associated with the circadian rhythms ( Weizman et al, 2019 ). In Hydra , Wnt signaling has been shown to play a vital role in the organizer formation and is associated with massive transcriptional changes ( Reddy et al, 2019 ).…”