Prof. César Arenas-Mena, The City University of New York
Prof. César Arenas-Mena, from The City University of New York, will present his latest work: "Transcriptional potency and the origins of developmental gene regulation".
Main content
Developmental potency is controlled by accessibility to transcriptional regulatory elements (TREs), that is, proximal promoters and distal enhancers/silencers. ATAC-seq during sea urchin development and differentiation reveals surprisingly early and widespread basal TRE accessibility that is not explained by concurrent or subsequent transcriptional activation, or by pioneer transcription factor binding sites. We are performing quantitative Micrococcal Nuclease, CUT&RUN and DNA sequence analysis to test the association of basal TRE accessibility with labile nucleosomes, multipotency histone variants H2A.Z and H3.3, and A/T sequence periodicities influencing nucleosomal interactions. We identify transcriptionally engaged TREs by Precision Run-On and sequencing (PRO-seq), which sharply maps the location of paused or elongating RNA polymerase Pol II genome-wide, as well as the transcription start sites (TSSs) that define TRE functional boundaries. Our analysis reveals that the majority of TRE accessibility changes during embryogenesis are transcriptional. We recently found that during sea urchin embryogenesis the majority of upregulated or downregulated promoters are controlled by transcription initiation changes rather than by pause/release shifts. Nevertheless, the relay of distal enhancer pause/release rates to proximal promoter transcription initiation rates seems feasible. I previously proposed the evolution of distal enhancers from inducible-type promoters, which diversified in distinct transcriptional states the ancestral constitutive expression of unicellular regulatory genes during the dawn of metazoans. In agreement, comparative PRO-seq analysis among holozoans reveals the evolution of new pause/release controls in metazoans that increased the combinatorial input code for developmental TREs to diversify transcriptional states.
