Enhancers

Motivation: Reversible epigenetic modifications that happen on the DNA's histones, namely histone modifications, play an important role in gene regulation by controlling the accessibility of different functional genomic regions. Such modifications have been measured and primarily studied on genes or their promoters, but a currently interesting and less studied category of functional elements are enhancers. Enhancer regions can be found virtually anywhere along our non-coding DNA and through looping towards the promoters of target genes they contribute to their normal expression patterns. Abnormal epigenetic signatures and somatic mutations in those regions can interfere with the en-hancer's looping procedure and result in irregular gene expression patterns, a crucial contributor in cancer development .

The mammalian radiation has corresponded with rapid changes in noncoding regions of the genome, but we lack a comprehensive understanding of regulatory evolution in mammals. Here, we track the evolution of promoters and enhancers active in liver across 20 mammalian species from six diverse orders by profiling genomic enrichment of H3K27 acetylation and H3K4 trimethylation. We report that rapid evolution of enhancers is a universal feature of mammalian genomes. Most of the recently evolved enhancers arise from ancestral DNA exaptation, rather than lineage-specific expansions of repeat elements. In contrast, almost all liver promoters are partially or fully conserved across these species. Our data further reveal that recently evolved enhancers can be associated with genes under positive selection, demonstrating the power of this approach for annotating regulatory adaptations in genomic sequences. These results provide important insight into the functional genetics underpinning mammali...

Neural circuitry for mating and reproduction resides within the terminal segments of central nervous system (CNS) which express Hox paralogous group 9-13 (in vertebrates) or Abdominal-B (Abd-B) in Drosophila. Terminal neuroblasts (NBs) in A8-A10 segments of Drosophila larval CNS are subdivided into two groups based on expression of transcription factor Doublesex (Dsx). While the sex specific fate of Dsx-positive NBs is well investigated, the fate of Dsx-negative NBs is not known so far. Our studies with Dsx-negative NBs suggests that these cells, like their abdominal counterparts (in A3-A7 segments) use Hox, Grai-nyhead (Grh) and Notch to undergo cell death during larval development. This cell death also happens by transcriptionally activating RHG family of apoptotic genes through a common apoptotic enhancer in early to mid L3 stages. However, unlike abdominal NBs (in A3-A7 segments) which use increasing levels of resident Hox factor Abdominal-A (Abd-A) as an apoptosis trigger, Dsx-negative NBs (in A8-A10 segments) keep the levels of resident Hox factor Abd-B constant. These cells instead utilize increasing levels of the temporal transcription factor Grh and a rise in Notch activity to gain apoptotic competence. Biochemical and in vivo analysis suggest that Abdominal-A and Grh binding motifs in the common apo-ptotic enhancer also function as Abdominal-B and Grh binding motifs and maintains the enhancer activity in A8-A10 NBs. Finally, the deletion of this enhancer by the CRISPR-Cas9 method blocks the apoptosis of Dsx-negative NBs. These results highlight the fact that Hox dependent NB apoptosis in abdominal and terminal regions utilizes common molecular players (Hox, Grh and Notch), but seems to have evolved different molecular strategies to pattern CNS. PLOS GENETICS PLOS Genetics | https://doi.org/10.1371/journal.pgen.

Histone-modifying enzymes are required for cell identity and lineage commitment, however
little is known about the regulatory origins of the epigenome during embryonic development.
Here we generate a comprehensive set of epigenome reference maps, which we use to
determine the extent to which maternal factors shape chromatin state in Xenopus embryos.
Using a-amanitin to inhibit zygotic transcription, we find that the majority of H3K4me3- and
H3K27me3-enriched regions form a maternally defined epigenetic regulatory space with an
underlying logic of hypomethylated islands. This maternal regulatory space extends to a
substantial proportion of neurula stage-activated promoters. In contrast, p300 recruitment to
distal regulatory regions requires embryonic transcription at most loci. The results show that
H3K4me3 and H3K27me3 are part of a regulatory space that exerts an extended maternal
control well into post-gastrulation development, and highlight the combinatorial action of
maternal and zygotic factors through proximal and distal regulatory sequences.