The landscape of histone modifications across 1% of the human genome in five human cell lines

Abstract

We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including the ENCODE Consortium common cell lines GM06990 (lymphoblastoid) and HeLa-S3, as well as K562, HFL-1, and MOLT4, we identified clear patterns of histone modification profiles with respect to genomic features. H3K4me3, H3K4me2, and H3ac modifications are tightly associated with the transcriptional start sites (TSSs) of genes, while H3K4me1 and H4ac have more widespread distributions. TSSs reveal characteristic patterns of both types of modification present and the position relative to TSSs. These patterns differ between active and inactive genes and in particular the state of H3K4me3 and H3ac modifications is highly predictive of gene activity. Away from TSSs, modification sites are enriched in H3K4me1 and relatively depleted in H3K4me3 and H3ac. Comparison between cell lines identified differences in the histone modification profiles associated with transcriptional differences between the cell lines. These results provide an overview of the functional relationship among histone modifications and gene expression in human cells.

Reassessing the abundance of H3K9me2 chromatin domains in embryonic stem cells

“…It is clear from visual inspection of the plots shown in Figure 1 and Supplementary Figure 1 that using a slightly lower cutoff threshold would have resulted in much greater concordance of domains between cell types. Hidden Markov model (HMM) algorithms are routinely used for detecting chromatin domains in binding data [2][3][4] , primarily because they do not rely on user-defined parameters and are therefore more objective. Similar to the binary classification (LOCK or not LOCK) that Wen et al applied, we applied a two-state HMM to the original datasets.…”

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide

“…Nearly half the DMRs contained at least one ENCODE feature ( Figure 3a). Histone 3 lysine 4 trimethylation (H3K4me3), a chromatin modification enriched in gene promoters and most often associated with euchromatin and active transcription 26 , and DNase I hypersensitivity sites (DHSs) which are associated with many cis-regulatory elements including promoters, enhancers, insulators, silencers and locus control regions 27 , overlapped most frequently with the DMRs (Figure 3b). Both features overlapped with 22.6% of DMRs.…”

Transcriptional Regulation of the Human Prostacyclin Receptor Gene Is Dependent on Sp1, PU.1 and Oct-1 in Megakaryocytes and Endothelial Cells

“…Chromatin immunoprecipitation (ChIP) assays were performed essentially as described by Kock et al, 2007 76 . Briefly, HEL cells (1 x 10 8 ) were grown in RPMI, 10 % FBS to 70 % confluency and collected by centrifugation at 2,000 g for 5 min at 4 o C, washed twice in ice-cold PBS and resuspended in 50 ml serumfree RPMI.…”