Comprehensive analysis of the chromatin landscape in Drosophila melanogaster

Abstract

Summary Chromatin is composed of DNA and a variety of modified histones and non-histone proteins, which impact cell differentiation, gene regulation and other key cellular processes. We present a genome-wide chromatin landscape for Drosophila melanogaster based on 18 histone modifications, summarized by 9 prevalent combinatorial patterns. Integrative analysis with other data (non-histone chromatin proteins, DNaseI hypersensitivity, GRO-seq reads produced by engaged polymerase, short/long RNA products) reveals discrete characteristics of chromosomes, genes, regulatory elements, and other functional domains. We find that active genes display distinct chromatin signatures that are correlated with disparate gene lengths, exon patterns, regulatory functions, and genomic contexts. We also demonstrate a diversity of signatures among Polycomb targets that include a subset with paused polymerase. This systematic profiling and integrative analysis of chromatin signatures provides insights into how genomic elements are regulated, and will serve as a resource for future experimental investigations of genome structure and function.

Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation

“…In the Drosophila heatshock protein 70 gene, FACT accumulates more in the distal transcribed region whereas Spt5 is enriched at the promoter-proximal region in association with RNAPII (37). In genome-wide studies, Spt5 occupancy appears to be proportional to the RNAPII occupancy (9, 17) whereas FACT enrichment is not necessarily associated with RNAPII (34). In the present study, we show that the site-specific accumulation of FACT and H3.3 at the SHM target regions in Ig genes may at least partly explain the mechanism of SHM targeting.…”

“…3 is not yet clearly understood, these two factors appear to accumulate at the same loci. A genome-wide study showed that FACT tends to accumulate at intragenic enhancer-like regions together with H3.3 in Drosophila cells (34). Furthermore, our ChIP analysis revealed that the distribution of SSRP1 and H3.3 on various genomic loci was highly overlapping.…”

Pioneer transcription factors in cell reprogramming

“…Here the data are mixed. First, recent studies indicate that ;40% of the mammalian and Droshophila genomes lack distinctive histone modifications and are considered to be in a ''low signal'' state (Kharchenko et al 2011;Ho et al 2014). Thus, other than being nucleosomal, a large fraction of chromatin appears to be neutralnot marked for either activation or repression.…”

Promoter architectures and developmental gene regulation

“…It was proposed that specific combinations of modifications at given locus form a so called "histone code", which is read by other proteins to bring about distinct downstream events [61]. High-resolution mapping of numerous histone modifications in multiple cell types contributed to detection of most common combinations and associated functional genomic elements [62][63][64] and allowed segmentation of the genome into distinct domains based on the levels of various modifications [62,63,65]. Although specific histone modification combinations generally reflect the identity of the underlying DNA element, recent study has shown that actual levels of modification do not necessarily reflect the predicted regulatory activity [66].…”