The TAGteam motif facilitates binding of 21 sequence-specific transcription factors in the <i>Drosophila</i> embryo

Satija, Rahul; Bradley, Robert K.

doi:10.1101/gr.130682.111

Cited by 49 publications

(45 citation statements)

References 41 publications

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“…An instructive role for ZLD in defining chromatin that is open and accessible to other factors (Harrison et al 2011) is further supported by its unusual property to bind to the majority (64%) of all occurrences of its sequence motif in the Drosophila genome (Harrison et al 2011). ZLD might thus be a prerequisite for both HOT regions (Nien et al 2011;Satija and Bradley 2012) and EEEs more generally. Similarly, a role for GAGA in nucleating or promoting the formation of TF complexes is consistent with its ability to self-oligomerize via its BTB/POZ domain (Espiná s et al 1999) and also form heteromeric complexes with the TF Tramtrack (Bardwell and Treisman 1994) and potentially other BTB/POZ domain-containing TFs (e.g., Abrupt, Bric-a-brac, Broad complex, and others).…”

Section: à303mentioning

confidence: 95%

“…Both TFs are maternally deposited into Drosophila embryos and are ubiquitously present at early stages. The transcriptional activator ZLD was recently shown to be an essential key activator of the early Drosophila zygotic genome (ten Bosch et al 2006;Liang et al 2008;Harrison et al 2011;Nien et al 2011) and a facilitator of overlapping TF-binding patterns (Satija and Bradley 2012), while GAGA is known as an enhancer of position effect variegation (PEV) (Farkas et al 1994), an anti-repressor (Croston et al 1991), and a factor required for creating and maintaining nuclease-hypersensitive regions (Lu et al 1993).…”

Section: à303mentioning

confidence: 99%

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HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature

Kvon¹,

Stampfel²,

et al. 2012

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HOT (highly occupied target) regions bound by many transcription factors are considered to be one of the most intriguing findings of the recent modENCODE reports, yet their functions have remained unclear. We tested 108 Drosophila melanogaster HOT regions in transgenic embryos with site-specifically integrated transcriptional reporters. In contrast to prior expectations, we found 102 (94%) to be active enhancers during embryogenesis and to display diverse spatial and temporal patterns, reminiscent of expression patterns for important developmental genes. Remarkably, HOT regions strongly activate nearby genes and are required for endogenous gene expression, as we show using bacterial artificial chromosome (BAC) transgenesis. HOT enhancers have a distinct cis-regulatory signature with enriched sequence motifs for the global activators Vielfaltig, also known as Zelda, and Trithoraxlike, also known as GAGA. This signature allows the prediction of HOT versus control regions from the DNA sequence alone. Here, we show that Drosophila HOT regions function as transcriptional enhancers with diverse activity patterns. While a large number of bound TFs is the defining feature of HOT regions, many TFs seem to be bound neutrally without any apparent contribution to enhancer activity. HOT enhancers are characterized by a distinct and predictive cis-regulatory signature, which includes motifs for Vielfaltig/Zelda (ZLD), a recently reported activator of the early Drosophila genome (Liang et al. 2008;Harrison et al. 2011;Nien et al. 2011), and Trithoraxlike/GAGA (GAGA), a TF known to form homomeric and heteromeric complexes (Bardwell and Treisman 1994) and to be required for the generation and maintenance of nucleosome-free regions (Croston et al. 1991;Nakayama et al. 2007). Results and Discussion HOT regions function as early embryonic enhancers with diverse patternsWe tested a representative set of 108 D. melanogaster HOT regions (see the Materials and Methods; Supplemental Tables 1, 2) in transgenic embryos with sitespecifically integrated transcriptional reporters (Fig. 1A). Strikingly, 94% (102) of these HOT regions drove reporter expression in a specific pattern during embryogenesis. In contrast, only 39% of control regions (16 of 41) functioned as enhancers, including 11 of 21 regions chosen to contain TF-binding sites and five of 20 regions chosen to contain no known binding sites (see the Materials and Methods; Supplemental Fig. S1; Supplemental Table 1). This enrichment of HOT over control regions is highest at stages 3-10 (corresponding to 1-5 h after fertilization) (Fig. 1B), at which most of the chromatin immunoprecipitation (ChIP) experiments leading to the definition of the HOT regions had been performed (MacArthur et al. 2009; The modENCODE Consortium 2010).Contrary to expectations that HOT enhancers might constitute a particular class of enhancers (for example, with ubiquitous activity), they display highly diverse spatial activity patterns in all major presumptive tissues of the blastoderm embryo ( Fig. 1C; Sup...

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Section: à303mentioning

confidence: 95%

Section: à303mentioning

confidence: 99%

HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature

Kvon¹,

Stampfel²,

et al. 2012

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“…This process of zygotic genome activation (ZGA) was thought to be under the control of many TFs with different roles in embryogenesis, but with the discovery of the "genome activators" in Drosophila (Vfl/Zld) (Liang et al 2008) and zebrafish (Nanog, Pou5f3, and SoxB1 family factors) (Lee et al 2013;Leichsenring et al 2013), it was realized that a single factor, or a small group of factors, could play a global role in genome activation. These factors bind to specific sequence motifs prior to ZGA (Harrison et al 2011;Leichsenring et al 2013); and in Drosophila, there is a striking correlation between Zld motifs and the magnitude and timing of zygotic gene expression during ZGA (Liang et al 2008;Harrison et al 2011;Nien et al 2011;Satija and Bradley 2012). Thus, these factors are thought to prime the genome for subsequent transcriptional activity.…”

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confidence: 99%

“…When the patterning TFs become active after 1 h, they bind in a pattern that correlates with their cognate motifs only when Zld motifs are present nearby (Satija and Bradley 2012).…”

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Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

et al. 2015

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The Drosophila genome activator Vielfaltig (Vfl), also known as Zelda (Zld), is thought to prime enhancers for activation by patterning transcription factors (TFs). Such priming is accompanied by increased chromatin accessibility, but the mechanisms by which this occurs are poorly understood. Here, we analyze the effect of Zld on genome-wide nucleosome occupancy and binding of the patterning TF Dorsal (Dl). Our results show that early enhancers are characterized by an intrinsically high nucleosome barrier. Zld tackles this nucleosome barrier through local depletion of nucleosomes with the effect being dependent on the number and position of Zld motifs. Without Zld, Dl binding decreases at enhancers and redistributes to open regions devoid of enhancer activity. We propose that Zld primes enhancers by lowering the high nucleosome barrier just enough to assist TFs in accessing their binding motifs and promoting spatially controlled enhancer activation if the right patterning TFs are present. We envision that genome activators in general will utilize this mechanism to activate the zygotic genome in a robust and precise manner.

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“…Drosophila HOT DNAs share certain sequence features, including GAGA elements (see below) and the TAGteam motif, which binds Zelda (Liang et al 2008;Satija and Bradley 2012). Like other regions containing these regulatory elements, HOT DNAs exhibit increased nucleosome turnover and histone H3.3, indicative of ''open'' chromatin (Jin et al 2005).…”

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confidence: 99%

HOT DNAs: a novel class of developmental enhancers: Figure 1.

Farley

Levine²

2012

Genes Dev.

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Enhancers mediate localized patterns of gene expression during development. A common feature of “traditional” enhancers is the presence of clustered binding motifs for sequence-specific transcription factors (TFs). In this issue of Genes & Development, Kvon and colleagues (pp. 908–913) present new evidence that HOT (highly occupied transcription) DNAs direct specific patterns of gene expression, despite being depleted for TF-binding motifs.

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The TAGteam motif facilitates binding of 21 sequence-specific transcription factors in the Drosophila embryo

Cited by 49 publications

References 41 publications

HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature

HOT regions function as patterned developmental enhancers and have a distinct cis-regulatory signature

Zelda overcomes the high intrinsic nucleosome barrier at enhancers during Drosophila zygotic genome activation

HOT DNAs: a novel class of developmental enhancers: Figure 1.

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