Establishment of regions of genomic activity during theDrosophilamaternal to zygotic transition

Abstract

We describe the genome-wide distributions and temporal dynamics of nucleosomes and post-translational histone modifications throughout the maternal-to-zygotic transition in embryos of Drosophila melanogaster. At mitotic cycle 8, when few zygotic genes are being transcribed, embryonic chromatin is in a relatively simple state: there are few nucleosome free regions, undetectable levels of the histone methylation marks characteristic of mature chromatin, and low levels of histone acetylation at a relatively small number of loci. Histone acetylation increases by cycle 12, but it is not until cycle 14 that nucleosome free regions and domains of histone methylation become widespread. Early histone acetylation is strongly associated with regions that we have previously shown to be bound in early embryos by the maternally deposited transcription factor Zelda, suggesting that Zelda triggers a cascade of events, including the accumulation of specific histone modifications, that plays a role in the subsequent activation of these sequences.

The degree of enhancer or promoter activity is reflected by the levels and directionality of eRNA transcription

“…Whether it is the process of enhancer transcription that is important (Wilson et al 1996;Cho et al 1998;Kaikkonen et al 2013) or the eRNA itself (Lam et al 2013;Melo et al 2013;Li et al 2014) may vary from one locus or context to another. Alternatively, it may be a nonfunctional consequence of the random engagement of Pol II to open chromatin (Struhl 2007).…”

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

“…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.…”

“…Thus, the low levels of H3K27ac and the reduced access to transcription factors that we observe for zen, dpp, and tld must be to some extent the result of Dl-mediated repression. (Li et al 2014) show that H3K27ac levels are accumulating early and gradually during development, and thus, some H3K27ac is present during enhancer priming by Zld at cell cycles 8 and 12. In contrast, H3K4me1 and H3K27me3, which mark poised enhancers, are only detectable after Dl-dependent transcription begins at stage 5 or cell cycle 14 (shaded in gray).…”

“…Based on a careful time-course analysis (Li et al 2014), the primed DV enhancers do not show the poised signature until cell cycle 14, when DV patterning begins. While H3K27ac accumulates very early and gradually, H3K4me1 and H3K27me3 show a strong increase only during cell cycle 14 (Fig.…”

“…Histone modification data during maternal-to-zygotic transition Processed H3K27ac, H3K4me1, and H3K27me3 ChIP-seq data in the early embryo (Li et al 2014) were obtained from GEO (GSE58935). ChIP-seq data are shown as average signal in a 1001-bp region centered at each enhancer.…”