Biology subjects

Arenas-Mena, C.

Publications and source records attributed to Arenas-Mena, C..

3 recordsLinked to original sources

bioRxiv2023

Accessibility and activity of transcriptional regulatory elements during sea urchin embryogenesis and differentiation

Transcriptional regulatory elements (TREs) are the primary nodes of the gene regulatory networks that control development. TREs are identified by PRO-seq and their accessibility by ATAC-seq during sea urchin embryonic development and differentiation. Our analysis identifies surprisingly early accessibility in 4-cell cleavage embryo TREs that is not necessarily followed by subsequent transcription, and an excess of ATAC-seq peaks transcriptionally disengaged during the stages analyzed. Embryonic accessibility shifts are driven by transcriptionally engaged TREs, and PRO-seq transcriptional differences at TREs provide more contrast among embryonic stages than ATAC-seq accessibility differences. TRE accessibility reaches a maximum around the 20-hour late blastula, which coincides with major embryo regionalizations. At the same time, a large number of distal TREs become transcriptionally disengaged, in support of an early Pol II primed model for developmental gene regulation that eventually resolves in transcriptional activation or silencing. A transcriptional potency model based on labile nucleosome TRE occupancy driven by DNA sequences and the prevalence of histone variants is proposed in order to explain the basal accessibility of transcriptionally inactive TREs during early embryogenesis. Summary statementGenomic profiles deciphering the location and activity of regulatory elements that control gene expression suggest general mechanisms of regulatory potency in early sea urchin embryos.

developmental biology↗

bioRxiv2023

Evolution of promoter-proximal pausing enabled a new layer of transcription control

Promoter-proximal pausing of RNA polymerase II (Pol II) is a key regulatory step during transcription. Despite the central role of pausing in gene regulation, we do not understand the evolutionary processes that led to the emergence of Pol II pausing or its transition to a rate-limiting step actively controlled by transcription factors. Here we analyzed transcription in species across the tree of life. Unicellular eukaryotes display a slow acceleration of Pol II near transcription start sites that transitioned to a longer-lived, focused pause in metazoans. This event coincided with the evolution of new subunits in the NELF and 7SK complexes. Depletion of NELF in mammals shifted the promoter-proximal buildup of Pol II from the pause site into the early gene body and compromised transcriptional activation for a set of heat shock genes. Our work details the evolutionary history of Pol II pausing and sheds light on how new transcriptional regulatory mechanisms evolve.

evolutionary biology↗

bioRxiv2021

Identification and prediction of developmental enhancers in sea urchin embryos

BackgroundThe transcription of developmental regulatory genes is often controlled by multiple cis-regulatory elements. The identification and functional characterization of distal regulatory elements remains challenging, even in tractable model organisms like sea urchins. ResultsWe evaluate the use of chromatin accessibility, transcription and RNA Polymerase II for their ability to predict enhancer activity of genomic regions in sea urchin embryos. ATAC-seq, PRO-seq, and Pol II ChIP-seq from early and late blastula embryos are manually contrasted with experimental cis-regulatory analyses available in sea urchin embryos, with particular attention to common developmental regulatory elements known to have enhancer and silencer functions differentially deployed among embryonic territories. Using the three functional genomic data types, machine learning models are trained and tested to classify and quantitatively predict the enhancer activity of several hundred genomic regions previously validated with reporter constructs in vivo. ConclusionsOverall, chromatin accessibility and transcription have substantial power for predicting enhancer activity. For promoter-overlapping cis-regulatory elements in particular, the distribution of Pol II is the best predictor of enhancer activity in blastula embryos. Furthermore, ATAC- and PRO-seq predictive value is stage dependent for the promoter-overlapping subset. This suggests that the sequence of regulatory mechanisms leading to transcriptional activation have distinct relevance at different levels of the developmental gene regulatory hierarchy deployed during embryogenesis.

genomics↗