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 and
morphogenetic events during organogenesis. Early embryonic patterning and
morphogenesis are regulated by the interplay between various maternally deposited as
well as zygotically transcribed RNA and protein determinants. However, understanding
of precise transcriptional mechanisms sculpting embryonic structures remains
inadequate. In the quest to identify novel mechanisms, here, we generated the lineagespecific
transcriptional and chromatin accessibility profiles of gastrulating embryos. Our
study highlighted Nodal signalling mediated dynamic chromatin remodelling activities
necessary for segregation of axial mesoderm and endoderm progenitors. Moreover, our
analysis offered an opportunity to identify and characterize understudied chromatin
organizers during germ layer segregation. We characterized the function of one such
lineage-restricted protein Satb2. Studies using transient knockdown allowed us to identify
a 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 enabled
us to dissect molecular mechanisms underlying pathological conditions associated with
satb2 mutation. Moreover, integrative analysis of the transcriptome, genome-wide
occupancy and chromatin accessibility revealed molecular interplays by which Satb2
performs contrasting functions during major gene regulatory transitions throughout early
embryogenesis. We found maternal Satb2 negatively regulate zygotic genes by
influencing the interplay between the pluripotency factors whereas, zygotic Satb2
activates the same group of genes during neural crest development. The comparative
analysis underscores how these antithetical activities are temporally coordinated and
functionally implemented. Taken together, our study highlights the evolutionary
implications of chromatin organization in the regulation of landmark developmental
transitions.
