Elucidating the role of chromatin organization during cell fate specification and vertebrate organogenesis

Abstract

The basic body plan is determined within hours to a few days of embryonic development This window is characterized by zygotic genome activation lineage specification andmorphogenetic events during organogenesis Early embryonic patterning andmorphogenesis are regulated by the interplay between various maternally deposited aswell as zygotically transcribed RNA and protein determinants However understandingof precise transcriptional mechanisms sculpting embryonic structures remainsinadequate In the quest to identify novel mechanisms here we generated the lineagespecifictranscriptional and chromatin accessibility profiles of gastrulating embryos Ourstudy highlighted Nodal signalling mediated dynamic chromatin remodelling activitiesnecessary for segregation of axial mesoderm and endoderm progenitors Moreover ouranalysis offered an opportunity to identify and characterize understudied chromatinorganizers during germ layer segregation We characterized the function of one suchlineage restricted protein Satb2 Studies using transient knockdown allowed us to identifya novel Wnt dependent role of Satb2 during early cell fate specification events Generation of tractable loss of function and gain of function models in zebrafish enabledus to dissect molecular mechanisms underlying pathological conditions associated withsatb2 mutation Moreover integrative analysis of the transcriptome genome wideoccupancy and chromatin accessibility revealed molecular interplays by which Satb2performs contrasting functions during major gene regulatory transitions throughout earlyembryogenesis We found maternal Satb2 negatively regulate zygotic genes byinfluencing the interplay between the pluripotency factors whereas zygotic Satb2activates the same group of genes during neural crest development The comparativeanalysis underscores how these antithetical activities are temporally coordinated and newline newline