Satb2 acts as a gatekeeper for major developmental transitions during early vertebrate embryogenesis

Saurabh J Pradhan,Mahendra Sonawane,Michael Smutny,Meghana S Oak,Sanjeev Galande,Girish Deshpande,Ojas Deshpande,Antonio J Giraldez,Yin Tang,Ankita Sharma,Puli Chandramouli Reddy,Carl-Philipp Heisenberg,Rini Shah,Greg Dsilva,Keisuke Sako,Rakesh Mishra,Mrinmoy Pal

doi:10.1038/s41467-021-26234-7

Abstract

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. ZGA is dependent upon dynamic chromatin architecture sculpted by conserved DNA-binding proteins. However, the direct mechanistic link between the onset of ZGA and the tissue-specific transcription remains unclear. Here, we have addressed the involvement of chromatin organizer Satb2 in orchestrating both processes during zebrafish embryogenesis. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb2. Maternal Satb2 prevents premature transcription of zygotic genes by influencing the interplay between the pluripotency factors. By contrast, zygotic Satb2 activates transcription of the same group of genes during neural crest development and organogenesis. Thus, our comparative analysis of maternal versus zygotic function of Satb2 underscores how these antithetical activities are temporally coordinated and functionally implemented highlighting the evolutionary implications of the biphasic and bimodal regulation of landmark developmental transitions by a single determinant.

Highlights

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities
To gain a detailed insight into the possible structural conservation among the SATB family proteins, we extracted the homologous sequence stretches by comparing their individual protein sequences
Our phylogenetic analysis revealed the presence of SATB homologs in two other invertebrates; Parasteatoda tepidariorum and Mizuhopecten yessoensis which include all three functional domains (Fig. 1a and Supplementary Fig. 1a)

Summary

Introduction

Zygotic genome activation (ZGA) initiates regionalized transcription underlying distinct cellular identities. Integrative analysis of transcriptome, genome-wide occupancy and chromatin accessibility reveals contrasting molecular activities of maternally deposited and zygotically synthesized Satb[2]. While ZGA is a conserved feature of early embryogenesis and relies upon genome-wide chromatin remodeling to establish transcriptional competence[13,14], how these genome-wide changes are translated into tissue-specific activities of patterning determinants remains largely unclear. We demonstrate that unlike its zygotic counterpart, the maternally deposited Satb[2] functions as a transcriptional repressor of zygotically transcribed genes and controls the timing of ZGA by differentially regulating pluripotency factors. Stagedependent transcription factor binding site (TFBS) prediction using genome-wide occupancy analysis has provided insights into mechanisms underlying the temporal activity of Satb[2]. Its ability to participate in different biological contexts likely depends on diverse protein interactions and the dynamic repertoire of genomic targets

Methods

Results

Conclusion