GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo
- University of Wisconsin-Madison, United States
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.
Data availability
Sequencing data have been deposited in GEO under accession code GSE152773.
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GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryoNCBI Gene Expression Omnibus, GSE152773.
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Zelda binding in the early Drosophila melanogasterNCBI Gene Expression Omnibus, GSE30757.
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The Genomic Binding Profile of GAGA Element Associated Factor (GAF) in Drosophila S2 cellsNCBI Gene Expression Omnibus, GSE40646.
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Targeting of the dosage-compensated male X-chromosome during early Drosophila developmentNCBI Gene Expression Omnibus, GSE133637.
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Establishment of regions of genomic activity during the Drosophila maternal-to-zygotic transitionNCBI Gene Expression Omnibus, GSE58935.
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Histone locus regulation by the Drosophila dosage compensation adaptor protein CLAMPNCBI Gene Expression Omnibus, GSE10292.
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Concentration dependent binding states of the Bicoid Homeodomain ProteinNCBI Gene Expression Omnibus, GSE86966.
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Continued activity of the pioneer factor Zelda is required to drive zygotic genome activationNCBI Gene Expression Omnibus, GSE121157.
Article and author information
Author details
Melissa M Harrison
Funding
National Institutes of Health (R01GM111694)
- Melissa M Harrison
National Institutes of Health (R35GM136298)
- Melissa M Harrison
Vallee Foundation
- Melissa M Harrison
National Institutes of Health (T32GM007215)
- Marissa M Gaskill
- Tyler J Gibson
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Gaskill et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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GAF is essential for zygotic genome activation and chromatin accessibility in the early Drosophila embryo
eLife 10:e66668.
https://doi.org/10.7554/eLife.66668
Further reading
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Gene regulation is essential for life and controlled by regulatory DNA. Mutations can modify the activity of regulatory DNA, and also create new regulatory DNA, a process called regulatory emergence. Non-regulatory and regulatory DNA contain motifs to which transcription factors may bind. In prokaryotes, gene expression requires a stretch of DNA called a promoter, which contains two motifs called –10 and –35 boxes. However, these motifs may occur in both promoters and non-promoter DNA in multiple copies. They have been implicated in some studies to improve promoter activity, and in others to repress it. Here, we ask whether the presence of such motifs in different genetic sequences influences promoter evolution and emergence. To understand whether and how promoter motifs influence promoter emergence and evolution, we start from 50 ‘promoter islands’, DNA sequences enriched with –10 and –35 boxes. We mutagenize these starting ‘parent’ sequences, and measure gene expression driven by 240,000 of the resulting mutants. We find that the probability that mutations create an active promoter varies more than 200-fold, and is not correlated with the number of promoter motifs. For parent sequences without promoter activity, mutations created over 1500 new –10 and –35 boxes at unique positions in the library, but only ~0.3% of these resulted in de-novo promoter activity. Only ~13% of all –10 and –35 boxes contribute to de-novo promoter activity. For parent sequences with promoter activity, mutations created new –10 and –35 boxes in 11 specific positions that partially overlap with preexisting ones to modulate expression. We also find that –10 and –35 boxes do not repress promoter activity. Overall, our work demonstrates how promoter motifs influence promoter emergence and evolution. It has implications for predicting and understanding regulatory evolution, de novo genes, and phenotypic evolution.
