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

Abstract

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.

Mll3 and Mll4 Facilitate Enhancer RNA Synthesis and Transcription from Promoters Independently of H3K4 Monomethylation

“…This pattern consists of a nucleosome depleted region, bound by transcription factors and coactivator complexes, and flanked by nucleosomes harboring specific histone modifications such as the monomethylation of histone H3 on lysine 4 (H3K4me1) and acetylation of histone H3 on lysine 27 (H3K27ac). Furthermore, H3K4me1 in the absence of H3K27ac (and, in some instances in the presence of the repressive mark H3K27me3) has been associated with enhancer states that are repressed or poised/primed for activation (Creyghton et al , 2010; Rada-Iglesias et al , 2011; Zentner, Tesar and Scacheri, 2011; Bonn et al , 2012; Koenecke et al , 2016). Importantly, a combination of H3K4me1/H3K27ac marks has been broadly utilized for epigenomic annotation of active enhancers in a myriad of biological contexts, facilitating systematic discovery and functional understanding of this important class of cis-regulatory elements (reviewed in Hardison and Taylor, 2012; Shlyueva, Stampfel and Stark, 2014).…”

Multi-level and lineage-specific interactomes of the Hox transcription factor Ubx contribute to its functional specificity

“…However, how multi-lineage TFs can function in such specific manner in different environments remains elusive. Most of the efforts to understand the function and specificity of TFs was so far focused on their interaction with regulatory proteins at cis-regulatory modules, so-called enhancers and promoters [5][6][7][8] . However, TFs do not only interact with other TFs but with a variety of proteins including chromatin associated proteins, histone modifiers, factors of the general transcriptional machinery or mRNA regulatory proteins [9][10][11][12][13] .…”

Odd-paired is a late-acting pioneer factor coordinating with Zelda to broadly regulate gene expression in early embryos

“…The unique histone methylation pattern exhibited by these classes of peaks, in particular, indicates that Opa targets are likely subject to later developmental regulation. The higher levels of H3K4me1 in the Opa-bound peaks could potentially also be connected to a poised state of late-acting enhancers (Koenecke et al, 2017) or because these regions correspond to other cis-regulatory elements, promoters or insulators, for example (Bonn et al, 2012; Rada-Iglesias et al, 2011) (see Discussion).…”