Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo

Sönmezer, Can; Kleinendorst, Rozemarijn; Imanci, Dilek; Barzaghi, Guido; Villacorta, Laura; Schübeler, Dirk; Beneš, Vladimı́r; Molina, Nacho; Krebs, Arnaud R

doi:10.1016/j.molcel.2020.11.015

Cited by 104 publications

(105 citation statements)

References 75 publications

(73 reference statements)

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“…5a, b). While these results need to be reproduced on other PFs, they propose that collaboration with multiple sequence-specific DNA-binding factors is needed to result in changes in the chromatin structure, in agreement with previous studies [40][41][42] .…”

Section: Resultssupporting

confidence: 90%

“…By definition, PF binding to condensed chromatin leads to increased accessibility of the surrounding region. Studies proposed several underlying mechanisms of this process: steric hindrance, recruitment of chromatin remodellers, or cooperativity with other TFs [37][38][39][40][41][42][43] . Our system has the advantage of allowing to assess the effect of PFs on chromatin accessibility, independent of their collaboration with other TFs, thanks to the absence of TFBSs in the vicinity of the tested motif.…”

Section: Resultsmentioning

confidence: 99%

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High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

et al. 2021

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Binding of mammalian transcription factors (TFs) to regulatory regions is hindered by chromatin compaction and DNA methylation of their binding sites. Nevertheless, pioneer transcription factors (PFs), a distinct class of TFs, have the ability to access nucleosomal DNA, leading to nucleosome remodelling and enhanced chromatin accessibility. Whether PFs can bind to methylated sites and induce DNA demethylation is largely unknown. Using a highly parallelized approach to investigate PF ability to bind methylated DNA and induce DNA demethylation, we show that the interdependence between DNA methylation and TF binding is more complex than previously thought, even within a select group of TFs displaying pioneering activity; while some PFs do not affect the methylation status of their binding sites, we identified PFs that can protect DNA from methylation and others that can induce DNA demethylation at methylated binding sites. We call the latter super pioneer transcription factors (SPFs), as they are seemingly able to overcome several types of repressive epigenetic marks. Finally, while most SPFs induce TET-dependent active DNA demethylation, SOX2 binding leads to passive demethylation, an activity enhanced by the co-binding of OCT4. This finding suggests that SPFs could interfere with epigenetic memory during DNA replication.

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Section: Resultssupporting

confidence: 90%

Section: Resultsmentioning

confidence: 99%

High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

et al. 2021

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“…Any TF with a response element close to the GAGAG binding site will profit from this increased accessibility ( 84 ). This indirect cooperativity does not rely on direct, physical interaction between TFs and, accordingly, is widely used in vivo ( 85 ).…”

Section: Discussionmentioning

confidence: 99%

Cell-free genomics reveal intrinsic, cooperative and competitive determinants of chromatin interactions

Eggers

Becker

2021

Nucleic Acids Research

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Metazoan transcription factors distinguish their response elements from a large excess of similar sequences. We explored underlying principles of DNA shape read-out and factor cooperativity in chromatin using a unique experimental system. We reconstituted chromatin on Drosophila genomes in extracts of preblastoderm embryos, mimicking the naïve state of the zygotic genome prior to developmental transcription activation. We then compared the intrinsic binding specificities of three recombinant transcription factors, alone and in combination, with GA-rich recognition sequences genome-wide. For MSL2, all functional elements reside on the X chromosome, allowing to distinguish physiological elements from non-functional ‘decoy’ sites. The physiological binding profile of MSL2 is approximated through interaction with other factors: cooperativity with CLAMP and competition with GAF, which sculpts the profile by occluding non-functional sites. An extended DNA shape signature is differentially read out in chromatin. Our results reveal novel aspects of target selection in a complex chromatin environment.

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“…Finally, the binding of multiple transcriptional activators to nucleosomal DNA at cis-regulatory elements (CREs) is inherently cooperative and can be critical to reaching a threshold response and a pattern in gene expression [ 169 ]. Interestingly, recent data from an in vivo quantitative detection of multiple transcription factors (TFs) at CREs measured genome-wide at the single-molecule level suggest that increased TF co-occupancy and cooperativity are required, but might not be sufficient, to open chromatin at sites of competition with nucleosomes, and that remodelers might be involved in TF co-occupancy [ 170 ]. The interplay between remodelers and TFs is of the utmost interest, and investigating the functions of accessory subunits of large remodelers in this context would be greatly beneficial.…”

Section: Shared and Specific Regulatory Principles And Features Governing The Sophisticated Conversations Between Nucleosomes And Remodelmentioning

confidence: 99%

Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer

Clapier

2021

IJMS

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The establishment and maintenance of genome packaging into chromatin contribute to define specific cellular identity and function. Dynamic regulation of chromatin organization and nucleosome positioning are critical to all DNA transactions—in particular, the regulation of gene expression—and involve the cooperative action of sequence-specific DNA-binding factors, histone modifying enzymes, and remodelers. Remodelers are molecular machines that generate various chromatin landscapes, adjust nucleosome positioning, and alter DNA accessibility by using ATP binding and hydrolysis to perform DNA translocation, which is highly regulated through sophisticated structural and functional conversations with nucleosomes. In this review, I first present the functional and structural diversity of remodelers, while emphasizing the basic mechanism of DNA translocation, the common regulatory aspects, and the hand-in-hand progressive increase in complexity of the regulatory conversations between remodelers and nucleosomes that accompanies the increase in challenges of remodeling processes. Next, I examine how, through nucleosome positioning, remodelers guide the regulation of gene expression. Finally, I explore various aspects of how alterations/mutations in remodelers introduce dissonance into the conversations between remodelers and nucleosomes, modify chromatin organization, and contribute to oncogenesis.

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Molecular Co-occupancy Identifies Transcription Factor Binding Cooperativity In Vivo

Cited by 104 publications

References 75 publications

High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

High throughput screening identifies SOX2 as a super pioneer factor that inhibits DNA methylation maintenance at its binding sites

Cell-free genomics reveal intrinsic, cooperative and competitive determinants of chromatin interactions

Sophisticated Conversations between Chromatin and Chromatin Remodelers, and Dissonances in Cancer

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