Transcriptional Activation Is a Conserved Feature of the Early Embryonic Factor Zelda That Requires a Cluster of Four Zinc Fingers for DNA Binding and a Low-complexity Activation Domain

Hamm, Danielle C.; Bondra, Eliana R.; Harrison, Melissa M.

doi:10.1074/jbc.m114.602292

Cited by 41 publications

(89 citation statements)

References 40 publications

(59 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Many transcription factors have strong activation domains, putting accessible enhancer regions at risk for unwarranted activation. For example, Zld has high transactivation potential and likely recruits the histone acetyl transferase CBP that mediates H3K27ac (Hamm et al 2015;Stampfel et al 2015), consistent with H3K27ac being present during enhancer priming by Zld (Li et al 2014). Strikingly, we showed that Zld is still bound to DV enhancers during DV patterning, yet these enhancers have no or low H3K27ac and remain uninduced in parts of the embryo.…”

Section: A Role For Repressors In Keeping Poised Enhancers Inactivementioning

confidence: 57%

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Koenecke

Johnston

et al. 2016

Genome Res.

View full text Add to dashboard Cite

Histone modifications are frequently used as markers for enhancer states, but how to interpret enhancer states in the context of embryonic development is not clear. The poised enhancer signature, involving H3K4me1 and low levels of H3K27ac, has been reported to mark inactive enhancers that are poised for future activation. However, future activation is not always observed, and alternative reasons for the widespread occurrence of this enhancer signature have not been investigated. By analyzing enhancers during dorsal-ventral (DV) axis formation in the Drosophila embryo, we find that the poised enhancer signature is specifically generated during patterning in the tissue where the enhancers are not induced, including at enhancers that are known to be repressed by a transcriptional repressor. These results suggest that, rather than serving exclusively as an intermediate step before future activation, the poised enhancer state may be a mark for spatial regulation during tissue patterning. We discuss the possibility that the poised enhancer state is more generally the result of repression by transcriptional repressors.

show abstract

Section: A Role For Repressors In Keeping Poised Enhancers Inactivementioning

confidence: 57%

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Koenecke

Johnston

et al. 2016

Genome Res.

View full text Add to dashboard Cite

show abstract

“…Instead, Zld binds DNA through a cluster of four zinc fingers in the C terminus (Struffi et al 2011;Hamm et al 2015). In addition, Zld is a large protein with no recognizable enzymatic domains that activates transcription through a low-complexity protein domain (Hamm et al 2015). Thus, Zld likely facilitates open chromatin through interactions with cofactors, and it is possible that recruitment of different cofactors to distinct Zld-bound loci could partially explain the differential requirement on Zld for chromatin accessibility in the early embryo.…”

Section: Genome Research 1721mentioning

confidence: 99%

“…Unlike the pioneer factor FOXA1, which can bind open chromatin by binding through a winged-helix domain (Cirillo et al 1998(Cirillo et al , 2002, the Zld DNAbinding domain does not resemble that of a linker histone. Instead, Zld binds DNA through a cluster of four zinc fingers in the C terminus (Struffi et al 2011;Hamm et al 2015). In addition, Zld is a large protein with no recognizable enzymatic domains that activates transcription through a low-complexity protein domain (Hamm et al 2015).…”

Section: Genome Research 1721mentioning

confidence: 99%

Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo

et al. 2015

Self Cite

View full text Add to dashboard Cite

The transition from a specified germ cell to a population of pluripotent cells occurs rapidly following fertilization. During this developmental transition, the zygotic genome is largely transcriptionally quiescent and undergoes significant chromatin remodeling. In Drosophila, the DNA-binding protein Zelda (also known as Vielfaltig) is required for this transition and for transcriptional activation of the zygotic genome. Open chromatin is associated with Zelda-bound loci, as well as more generally with regions of active transcription. Nonetheless, the extent to which Zelda influences chromatin accessibility across the genome is largely unknown. Here we used formaldehyde-assisted isolation of regulatory elements to determine the role of Zelda in regulating regions of open chromatin in the early embryo. We demonstrate that Zelda is essential for hundreds of regions of open chromatin. This Zelda-mediated chromatin accessibility facilitates transcription-factor recruitment and early gene expression. Thus, Zelda possesses some key characteristics of a pioneer factor. Unexpectedly, chromatin at a large subset of Zelda-bound regions remains open even in the absence of Zelda. The GAGA factor-binding motif and embryonic GAGA factor binding are specifically enriched in these regions. We propose that both Zelda and GAGA factor function to specify sites of open chromatin and together facilitate the remodeling of the early embryonic genome.

show abstract

“…Although the exact mechanism by which ZLD mediates BCD hub formation and binding remains unclear, we speculate that a combination of protein-protein interactions facilitated by intrinsically disordered low-complexity domains (Hamm et al 2015) of ZLD and its reported role in promoting chromatin accessibility (Foo et al 2014;Schulz et al 2015;Sun et al 2015) may contribute to BCD clustering (Fig. 4).…”

Section: Formation Of Bcd Hubs In the Posterior Embryo Is Dependent Omentioning

confidence: 99%

Dense Bicoid hubs accentuate binding along the morphogen gradient

et al. 2017

View full text Add to dashboard Cite

Morphogen gradients direct the spatial patterning of developing embryos; however, the mechanisms by which these gradients are interpreted remain elusive. Here we used lattice light-sheet microscopy to perform in vivo singlemolecule imaging in early Drosophila melanogaster embryos of the transcription factor Bicoid that forms a gradient and initiates patterning along the anteroposterior axis. In contrast to canonical models, we observed that Bicoid binds to DNA with a rapid off rate throughout the embryo such that its average occupancy at target loci is on-ratedependent. We further observed Bicoid forming transient "hubs" of locally high density that facilitate binding as factor levels drop, including in the posterior, where we observed Bicoid binding despite vanishingly low protein levels. We propose that localized modulation of transcription factor on rates via clustering provides a general mechanism to facilitate binding to low-affinity targets and that this may be a prevalent feature of other developmental transcription factors.

show abstract

Transcriptional Activation Is a Conserved Feature of the Early Embryonic Factor Zelda That Requires a Cluster of Four Zinc Fingers for DNA Binding and a Low-complexity Activation Domain

Cited by 41 publications

References 40 publications

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Drosophilapoised enhancers are generated during tissue patterning with the help of repression

Zelda is differentially required for chromatin accessibility, transcription factor binding, and gene expression in the early Drosophila embryo

Dense Bicoid hubs accentuate binding along the morphogen gradient

Contact Info

Product

Resources

About