GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo
Curation statements for this article:-
Curated by eLife
Evaluation Summary:
This paper will be of interest to a broad audience of developmental biologists and molecular biologists in the field of transcriptional control and epigenetics. It evaluates the pioneer factor activity associated with GAGA-Factor during the process of zygotic genome activation. The experiments are rigorously performed and the data analysis supports the conclusions.
This manuscript is in revision at eLife.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors)
This article has been Reviewed by the following groups
Discuss this preprint
Start a discussion What are Sciety discussions?Listed in
- Evaluated articles (eLife)
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.
Article activity feed
-
Reviewer #2 (Public Review):
This work evaluates the role for GAGA factor (GAF) as a pioneer factor during the zygotic genome activation (ZGA) of early Drosophila embryogenesis. GAF has previously been shown to regulate chromatin accessibility and higher order genome organization in a variety of biological contexts. However, it has historically been difficult to evaluate the role of GAF specifically during early embryogenesis through standard genetic approaches. This paper solves this problem by employing a combination of gene editing and targeted degradation strategies to specifically knock down GAF in early embryos. Through a combination of imaging and genomic approaches, this paper demonstrates a population of genomic loci that depend on GAF to gain chromatin accessibility and to be expressed during the maternal to zygotic …
Reviewer #2 (Public Review):
This work evaluates the role for GAGA factor (GAF) as a pioneer factor during the zygotic genome activation (ZGA) of early Drosophila embryogenesis. GAF has previously been shown to regulate chromatin accessibility and higher order genome organization in a variety of biological contexts. However, it has historically been difficult to evaluate the role of GAF specifically during early embryogenesis through standard genetic approaches. This paper solves this problem by employing a combination of gene editing and targeted degradation strategies to specifically knock down GAF in early embryos. Through a combination of imaging and genomic approaches, this paper demonstrates a population of genomic loci that depend on GAF to gain chromatin accessibility and to be expressed during the maternal to zygotic transition. This work identifies an additional pioneer factor activity operating at ZGA and furthermore evaluates the potential interdependency of GAF and another pioneer, Zelda.
-
Evaluation Summary:
This paper will be of interest to a broad audience of developmental biologists and molecular biologists in the field of transcriptional control and epigenetics. It evaluates the pioneer factor activity associated with GAGA-Factor during the process of zygotic genome activation. The experiments are rigorously performed and the data analysis supports the conclusions.
This manuscript is in revision at eLife.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors)
-
