ATAC-seq footprinting unravels kinetics of transcription factor binding during zygotic genome activation

AbstractWhile footprinting analysis of ATAC-seq data can theoretically enable investigation of transcription factor (TF) binding, the lack of a computational tool able to conduct different levels of footprinting analysis has so-far hindered the widespread application of this method. Here we present TOBIAS, a comprehensive, accurate, and fast footprinting framework enabling genome-wide investigation of TF binding dynamics for hundreds of TFs simultaneously. As a proof-of-concept, we illustrate how TOBIAS can unveil complex TF dynamics during zygotic genome activation (ZGA) in both humans and mice, and explore how zygotic Dux activates cascades of TFs, binds to repeat elements and induces expression of novel genetic elements. TOBIAS is freely available at: https://github.com/loosolab/TOBIAS.

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Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

10.1101/125716 ◽

2017 ◽

Author(s):

Shai R. Joseph ◽

Máté Pálfy ◽

Lennart Hilbert ◽

Mukesh Kumar ◽

Jens Karschau ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Dna Binding ◽

Transcription Factor Binding ◽

Factor Binding ◽

Zygotic Transcription ◽

Maternal To Zygotic Transition ◽

Nucleosome Density ◽

Core Histones ◽

Genome Activation

SUMMARYUpon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

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CLAMP and Zelda function together to promote Drosophila zygotic genome activation

eLife ◽

10.7554/elife.69937 ◽

2021 ◽

Vol 10 ◽

Author(s):

Jingyue Duan ◽

Leila Rieder ◽

Megan M Colonnetta ◽

Annie Huang ◽

Mary Mckenney ◽

...

Keyword(s):

Transcription Factor ◽

Embryonic Development ◽

Essential Role ◽

Chromatin Accessibility ◽

Zygotic Genome Activation ◽

Zygotic Transcription ◽

Pioneer Factor ◽

Pioneer Transcription Factor ◽

Genome Activation ◽

Zygotic Genome

During the essential and conserved process of zygotic genome activation (ZGA), chromatin accessibility must increase to promote transcription. Drosophila is a well-established model for defining mechanisms that drive ZGA. Zelda (ZLD) is a key pioneer transcription factor (TF) that promotes ZGA in the Drosophila embryo. However, many genomic loci that contain GA-rich motifs become accessible during ZGA independent of ZLD. Therefore, we hypothesized that other early TFs that function with ZLD have not yet been identified, especially those that are capable of binding to GA-rich motifs such as CLAMP. Here, we demonstrate that Drosophila embryonic development requires maternal CLAMP to: 1) activate zygotic transcription; 2) increase chromatin accessibility at promoters of specific genes that often encode other essential TFs; 3) enhance chromatin accessibility and facilitate ZLD occupancy at a subset of key embryonic promoters. Thus, CLAMP functions as a pioneer factor which plays a targeted yet essential role in ZGA.

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Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

eLife ◽

10.7554/elife.23326 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 60

Author(s):

Shai R Joseph ◽

Máté Pálfy ◽

Lennart Hilbert ◽

Mukesh Kumar ◽

Jens Karschau ◽

...

Keyword(s):

Transcription Factor ◽

Transcription Factors ◽

Dna Binding ◽

Transcription Factor Binding ◽

Factor Binding ◽

Zygotic Transcription ◽

Maternal To Zygotic Transition ◽

Nucleosome Density ◽

Core Histones ◽

Genome Activation

Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

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