Comparative analysis of metazoan chromatin organization.

Nature
Authors
Keywords
Abstract

Genome function is dynamically regulated in part by chromatin, which consists of the histones, non-histone proteins and RNA molecules that package DNA. Studies in Caenorhabditis elegans and Drosophila melanogaster have contributed substantially to our understanding of molecular mechanisms of genome function in humans, and have revealed conservation of chromatin components and mechanisms. Nevertheless, the three organisms have markedly different genome sizes, chromosome architecture and gene organization. On human and fly chromosomes, for example, pericentric heterochromatin flanks single centromeres, whereas worm chromosomes have dispersed heterochromatin-like regions enriched in the distal chromosomal 'arms', and centromeres distributed along their lengths. To systematically investigate chromatin organization and associated gene regulation across species, we generated and analysed a large collection of genome-wide chromatin data sets from cell lines and developmental stages in worm, fly and human. Here we present over 800 new data sets from our ENCODE and modENCODE consortia, bringing the total to over 1,400. Comparison of combinatorial patterns of histone modifications, nuclear lamina-associated domains, organization of large-scale topological domains, chromatin environment at promoters and enhancers, nucleosome positioning, and DNA replication patterns reveals many conserved features of chromatin organization among the three organisms. We also find notable differences in the composition and locations of repressive chromatin. These data sets and analyses provide a rich resource for comparative and species-specific investigations of chromatin composition, organization and function.

Year of Publication
2014
Journal
Nature
Volume
512
Issue
7515
Pages
449-52
Date Published
2014 Aug 28
ISSN
1476-4687
URL
DOI
10.1038/nature13415
PubMed ID
25164756
PubMed Central ID
PMC4227084
Links
Grant list
5RL9EB008539 / EB / NIBIB NIH HHS / United States
U54 HG006991 / HG / NHGRI NIH HHS / United States
54523 / Wellcome Trust / United Kingdom
R01 HG004037 / HG / NHGRI NIH HHS / United States
U54CA121852 / CA / NCI NIH HHS / United States
U01HG004270 / HG / NHGRI NIH HHS / United States
092096 / Wellcome Trust / United Kingdom
T32 HG002295 / HG / NHGRI NIH HHS / United States
U01HG004279 / HG / NHGRI NIH HHS / United States
U01HG004695 / HG / NHGRI NIH HHS / United States
R01 GM034059 / GM / NIGMS NIH HHS / United States
RL9 EB008539 / EB / NIBIB NIH HHS / United States
U01 HG004279 / HG / NHGRI NIH HHS / United States
R37 GM048405 / GM / NIGMS NIH HHS / United States
U54 CA121852 / CA / NCI NIH HHS / United States
U54 HG004570 / HG / NHGRI NIH HHS / United States
T32 GM071340 / GM / NIGMS NIH HHS / United States
Howard Hughes Medical Institute / United States
101863 / Wellcome Trust / United Kingdom
U01HG004258 / HG / NHGRI NIH HHS / United States
U01 HG004258 / HG / NHGRI NIH HHS / United States
U01 HG004270 / HG / NHGRI NIH HHS / United States
U54HG004570 / HG / NHGRI NIH HHS / United States
K99HG006259 / HG / NHGRI NIH HHS / United States
U01 HG004695 / HG / NHGRI NIH HHS / United States
K99 HG006259 / HG / NHGRI NIH HHS / United States
R01 GM098461 / GM / NIGMS NIH HHS / United States