GAGA factor: a multifunctional pioneering chromatin protein

Chetverina, Darya; Erokhin, Maksim; Schedl, Paul

doi:10.1007/s00018-021-03776-z

Cited by 45 publications

(33 citation statements)

References 141 publications

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“…GAF is known to be present on both active and repressive chromatin regions (Adkins et al 2006; Chetverina et al 2021). We therefore assessed the chromatin landscape of GAF mitotically retained regions.…”

Section: Resultsmentioning

confidence: 99%

“…Multiple experiments, with model genes in vitro (e.g. hsp70, hsp26) or from genome-wide approaches clearly demonstrated that GAF contributes to generate nucleosome-free regions (Chetverina et al 2021). The general view is that this capacity is permitted though the interaction of GAF with nucleosome remodeling factors as PBAP (SWI/SNIF), NURF (ISWI) (Judd et al 2021) or FACT (Orphanides et al 1998). Although not yet confirmed with live imaging, immuno-staining data suggest that NURF is removed during metaphase but re-engages chromatin by anaphase (Kwon et al 2021).…”

Section: Discussionmentioning

confidence: 99%

“…Here we asked whether GAF acts as a mitotic bookmarker during ZGA. GAF, encoded by the Trithorax-like gene, binds to repeating (GA) n sequences and displays a broad set of functions including gene activation or silencing, nucleosome remodeling and chromatin organization (Chetverina et al 2021). In addition, GAF has been shown to be enriched at paused promoters (Li and Gilmour 2013) and its manipulation in Drosophila S2 cells demonstrated a capacity to rapidly evict nucleosomes, thereby facilitating the recruitment of Pol II at promoters (Fuda et al 2015; Judd et al 2021).…”

Section: Introductionmentioning

confidence: 99%

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The control of transcriptional memory by stable mitotic bookmarking

Bellec

Dufourt

Hunt

et al. 2021

Preprint

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To maintain cellular identities during development, gene expression profiles must be faithfully propagated through cell generations. The reestablishment of gene expression patterns upon mitotic exit is thought to be mediated, in part, by mitotic bookmarking by transcription factors (TF). However, the mechanisms and functions of TF mitotic bookmarking during early embryogenesis remain poorly understood. In this study, taking advantage of the naturally synchronized mitoses of Drosophila early embryos, we provide evidence that the pioneer-like transcription factor GAF acts as stable mitotic bookmarker during zygotic genome activation. We report that GAF remains associated to a large fraction of its interphase targets including at cis-regulatory sequences of key developmental genes, with both active and repressive chromatin signatures. GAF mitotic targets are globally accessible during mitosis and are bookmarked via histone acetylation (H4K8ac). By monitoring the kinetics of transcriptional activation in living embryos, we provide evidence that GAF binding establishes competence for rapid activation upon mitotic exit.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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The control of transcriptional memory by stable mitotic bookmarking

Bellec

Dufourt

Hunt

et al. 2021

Preprint

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“…The ftzΔZ deletion described above removed the zebra element from position -670 at the 5′ end, as defined by Hiromi et al (1985) and Dearolf et al (1989a , 1989b ), to position -74 at the 3′ end (see Figure 1 ). Although the ftz basal promoter had previously been defined as requiring sequences to -40 ( Dearolf et al 1989b ), our genome edit left intact additional sequence that includes a potential binding site for the chromatin remodeling protein GAGA Factor ( Topol et al 1991 ), which could influence basal promoter accessibility ( Judd et al 2021 ; reviewed in Chetverina et al 2021 ). To ensure that the choice of the -74 position for the zebra element deletion did not inadvertently leave intact patterning information for ftz stripes, we generated two reporter genes: zebra-40 includes sequences between -670 and -41 ( zebra-40 ), whereas zebra-73 includes sequences between -670 and -74.…”

Section: Resultsmentioning

confidence: 99%

The fushi tarazu zebra element is not required for Drosophila viability or fertility

Graham

Fischer

Giri

et al. 2021

G3 Genes|Genomes|Genetics

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Expression of genes in precisely controlled spatiotemporal patterns is essential for embryonic development. Much of our understanding of mechanisms regulating gene expression comes from the study of cis-regulatory elements (CREs) that direct expression of reporter genes in transgenic organisms. This reporter-transgene approach identifies genomic regions sufficient to drive expression but fails to provide information about quantitative and qualitative contributions to endogenous expression, although such conclusions are often inferred. Here we evaluated the endogenous function of a classic Drosophila CRE, the fushi tarazu (ftz) zebra element. ftz is a pair-rule segmentation gene expressed in seven stripes during embryogenesis, necessary for formation of alternate body segments. Reporter transgenes identified the promoter-proximal zebra element as a major driver of the seven ftz stripes. We generated a precise genomic deletion of the zebra element (ftzΔZ) to assess its role in the context of native chromatin and neighboring CREs, expecting large decreases in ftz seven-stripe expression. However, significant reduction in expression was found for only one stripe, ftz stripe 4, expressed at ∼25% of wild type levels in ftzΔZ homozygotes. Defects in corresponding regions of ftzΔZ mutants suggest this level of expression borders the threshold required to promote morphological segmentation. Further, we established true-breeding lines of homozygous ftzΔZ flies, demonstrating that the body segments missing in the mutants are not required for viability or fertility. These results highlight the different types of conclusions drawn from different experimental designs and emphasize the importance of examining transcriptional regulatory mechanisms in the context of the native genomic environment.

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“…the sustained opening of chromatin, requires the joint activities of sequence-specific DNA-binding factors and ATP-dependent remodeling enzymes 12,19,24,25,73,74 , the latter proteins interacting with chromatin with a lifetime of seconds 67,69,70 . GAF directs pioneering functions not only by virtue of its affinity for nucleosomal DNA targets 12,75 but also recruitment of chromatin remodelers 12,14,15,24,42,76 . Given the highly transient association and variable occupancy levels displayed by remodelers 67,70 , we hypothesized that GAF should instead sustain high occupancy along with protracted dwell time to continuously maintain open chromatin at cognate targets .…”

Section: Constitutively High Temporal Occupancy Defines Pioneering Activitymentioning

confidence: 99%

Kinetic principles underlying pioneer function of GAGA transcription factor in live cells

Tang

et al. 2021

Preprint

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How pioneer factors interface with chromatin to promote accessibility for transcription control is poorly understood in vivo. Here, we directly visualize chromatin association by the prototypical GAGA pioneer factor (GAF) in live Drosophila hemocytes. Single-particle tracking reveals that the majority of GAF is chromatin-bound, with a stable-binding fraction showing nucleosome-like confinement residing on chromatin for over 2 minutes, far longer than the dynamic range of most transcription factors. These kinetic properties require the full complement of GAF's DNA-binding, multimerization and intrinsically disordered domains, and are autonomous from recruited chromatin remodelers NURF and PBAP, whose activities primarily benefit GAF's neighbors such as HSF. Evaluation of GAF kinetics together with its endogenous abundance indicates that despite on-off dynamics, GAF constitutively and fully occupies chromatin targets, thereby providing a temporal mechanism that sustains open chromatin for transcriptional responses to homeostatic, environmental, and developmental signals.

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GAGA factor: a multifunctional pioneering chromatin protein

Cited by 45 publications

References 141 publications

The control of transcriptional memory by stable mitotic bookmarking

The control of transcriptional memory by stable mitotic bookmarking

The fushi tarazu zebra element is not required for Drosophila viability or fertility

Kinetic principles underlying pioneer function of GAGA transcription factor in live cells

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