Genome-wide maps of chromatin state in pluripotent and lineage-committed cells

Abstract

We report the application of single molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over 4 billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 tri-methylation effectively discriminate genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 tri-methylation marks primary coding and non-coding transcripts, facilitating gene annotation. Lysine 9 and lysine 20 tri-methylation are detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 tri-methylation mark imprinting control regions. Finally, we show that chromatin state can be read in an allelespecific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.

Analysis of opo cis-regulatory landscape uncovers Vsx2 requirement in early eye morphogenesis

“…This suggests that opo has a complex regulatory input, as previously reported for other developmental genes 40 . For each CNE, we then examined the co-occurrence of the predictive enhancer epigenetic marks H3K4me1 and H3K27ac, as determined in previous chromatin immunoprecipitation (ChIP)-Seq studies in human cell lines 41,42 and, for their homologous regions, in zebrafish embryos 43 . These analyses revealed that a large majority of the identified CNEs (21 out of 23) overlap with regions labelled with at least one epigenetic mark, either in human cell lines, zebrafish embryos or both (Supplementary Table 2), suggesting that these conserved regions may act as enhancers.…”

“…A total of 24 conserved CNEs were selected within the opo locus using VISTA Browser 65 and taking as a reference the human genome (NCBI36/hg18) and the default parameters (Z100 bp and Z70% identity). The presence of predictive epigenetic marks for enhancer activity 66 that overlap opo-associated CNEs was evaluated using available data from human cell lines 41,42 and zebrafish embryos 43 . As a reference, four non-conserved elements marked with H3K4me1 and H3K27ac signals in human cell lines were also tested in our enhancer screening.…”

Aging by epigenetics—A consequence of chromatin damage?

“…Third, remarkably and paradoxically, formation of heterochromatin actually depends on a degree of transcription, which contributes to heterochromatinization through the RNAi pathway [4]. Consistent with this, recent genome-wide analyses have shown that virtually all DNA nucleotides of the human genome are, to some degree, transcribed into RNA [13][14][15]. Indeed, telomeric heterochromatin was recently shown to be transcribed [16,17].…”

Histone H4 lysine 20 monomethylation promotes transcriptional repression by L3MBTL1

“…H4K20me1 is associated with facultative heterochromatin (Fang et al, 2002;Martens et al, 2005;Sims et al, 2006), and the inactive X chromosome (Kohlmaier et al, 2004). In contrast, H4K20me3 marks constitutive heterochromatin (Schotta et al, 2004;Mikkelsen et al, 2007).…”