GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo.

Marissa M Gaskill,Elizabeth D Larson,Melissa M Harrison,Tyler J Gibson

doi:10.7554/elife.66668

Abstract

Following fertilization, the genomes of the germ cells are reprogrammed to form the totipotent embryo. Pioneer transcription factors are essential for remodeling the chromatin and driving the initial wave of zygotic gene expression. In Drosophila melanogaster, the pioneer factor Zelda is essential for development through this dramatic period of reprogramming, known as the maternal-to-zygotic transition (MZT). However, it was unknown whether additional pioneer factors were required for this transition. We identified an additional maternally encoded factor required for development through the MZT, GAGA Factor (GAF). GAF is necessary to activate widespread zygotic transcription and to remodel the chromatin accessibility landscape. We demonstrated that Zelda preferentially controls expression of the earliest transcribed genes, while genes expressed during widespread activation are predominantly dependent on GAF. Thus, progression through the MZT requires coordination of multiple pioneer-like factors, and we propose that as development proceeds control is gradually transferred from Zelda to GAF.

Highlights

Pronounced changes in cellular identity are driven by pioneer transcription factors that act at the top of gene regulatory networks
No peaks were called in the w1118 dataset for either stage, confirming the specificity of the peaks identified in the GAGA Factor (GAF)-super folder Green Fluorescent Protein (sfGFP)(C) embryos (Figure 1 – figure supplement 2 A,B)
Peaks were enriched at promoters, which fits with the previously defined role of GAF in establishing paused RNA polymerase (Figure 1 – figure supplement 2C) (Lee et al 2008; Fuda et al 2015; Judd et al 2021). 197 There was a substantial degree of overlap between GAF peaks identified at both stage 3 and stage 5. 2,955 peaks were shared between the two time points, representing 87% of total stage 3 peaks and 71% of total stage 5 peaks (Figure 1C, D, Figure 1 – figure supplement 2D)

Summary

Introduction

Pronounced changes in cellular identity are driven by pioneer transcription factors that act at the top of gene regulatory networks. Analysis of hypomorphic alleles has suggested an important function for GAF in the early embryo in both driving expression of Ultrabiothorax (Ubx), Abdominal B (Abd-B), engrailed (en), and fushi tarazu (ftz) and in maintaining normal embryonic development (Bhat et al 1996; Farkas et al 1994) Given these diverse functions for GAF, and that it shares many properties of a pioneer transcription factor, we sought to investigate whether it has a global role in reprogramming the zygotic genome for transcriptional activation. At least two pioneer-like transcription factors, Zld and GAF, must cooperate to reprogram the zygotic genome of Drosophila following fertilization. 150

Results

Discussion

Materials and Methods

982 Acknowledgments