A clustering approach for identification of enriched domains from histone modification ChIP-Seq data

Zang, Chongzhi; Schones, Dustin E.; Zeng, Chen; Cui, Kairong; Zhao, Keji; Peng, Weiqun

doi:10.1093/bioinformatics/btp340

Cited by 964 publications

(931 citation statements)

References 39 publications

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“…For each MSC sample, peak calls were made for each histone modification using SICER. 51 Consensus peaks for each histone modification were then generated by identifying peaks present in at least 2 of the 3 samples. Genomic cis-regulatory elements were defined by the co-localization of the constitutive different histone modifications characterizing each element (Table S2).…”

Section: Resultsmentioning

confidence: 99%

Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status

et al. 2015

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Osteosarcoma is the most common primary malignant bone tumor in children. Validated biological markers for disease prognosis available at diagnosis are lacking. No genome-wide DNA methylation studies linked to clinical outcomes have been reported in osteosarcoma to the best of our knowledge. To address this, we tested the methylome at over 1.1 million loci in 15 osteosarcoma biopsy samples obtained prior to the initiation of therapy and correlated these molecular data with disease outcomes. At more than 17% of the tested loci, samples obtained from patients who experienced disease relapse were more methylated than those from patients who did not have recurrence while patients who did not experience disease relapse had more DNA methylation at fewer than 1%. In samples from patients who went on to have recurrent disease, increased DNA methylation was found at gene bodies, intergenic regions and empirically-annotated candidate enhancers, whereas candidate gene promoters were unusual for a more balanced distribution of increased and decreased DNA methylation with 6.6% of gene promoter loci being more methylated and 2% of promoter loci being less methylated in patients with disease relapse. A locus at the TLR4 gene demonstrates one of strongest associations between DNA methylation and 5 y event-free survival (P-value D 1.7 £ 10 ¡6 ), with empirical annotation of this locus showing promoter characteristics. Our data indicate that DNA methylation information has the potential to be predictive of outcome in pediatric osteosarcoma, and that both promoters and non-promoter loci are potentially informative in DNA methylation studies.

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Section: Resultsmentioning

confidence: 99%

Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status

et al. 2015

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“…Unlike transcription factors and certain other histone modifications, H3K27me3 forms broad patterns of enrichment that are of indeterminate length (genome-wide analysis has shown these to be up to ;100 kb in Drosophila) (Papp and Müller 2006;Kharchenko et al 2011;Nègre et al 2011), and therefore simple peak-based analysis is not a suitable analysis method (Xiao et al 2012). Because of the many distinct cell types of a Drosophila puparium, it is also not appropriate to treat H3K27me3 as a binary modification of chromatin (Zang et al 2009). Therefore we chose to analyze the data quantitatively, using the number of sequence reads falling within prespecified intervals (e.g., the exons of a gene) as an indication of the overall level of H3K27me3 signal within a region (Supplemental Fig.…”

Section: Resultsmentioning

confidence: 99%

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Arthur

Slattery

et al. 2014

Genome Res.

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Histone modifications are critical for the regulation of gene expression, cell type specification, and differentiation. However, evolutionary patterns of key modifications that regulate gene expression in differentiating organisms have not been examined. Here we mapped the genomic locations of the repressive mark histone 3 lysine 27 trimethylation (H3K27me3) in four species of Drosophila, and compared these patterns to those in C. elegans. We found that patterns of H3K27me3 are highly conserved across species, but conservation is substantially weaker among duplicated genes. We further discovered that retropositions are associated with greater evolutionary changes in H3K27me3 and gene expression than tandem duplications, indicating that local chromatin constraints influence duplicated gene evolution. These changes are also associated with concomitant evolution of gene expression. Our findings reveal the strong conservation of genomic architecture governed by an epigenetic mark across distantly related species and the importance of gene duplication in generating novel H3K27me3 profiles.[Supplemental material is available for this article.]While transcriptional regulation has long been recognized as a significant target of evolutionary change (King and Wilson 1975), the specific mechanisms behind regulatory divergence have been difficult to dissect (Carroll 2008). In most cases, research has focused on recognizable cis-elements where transcription factors bind in a sequence-specific manner (Borneman et al. 2007;Bradley et al. 2010;Dowell 2010;Ni et al. 2012). Changes to either a transcription factor's DNA-binding properties or transcription factor binding sites (TFBS) enable the evolution of differential regulation, and numerous examples of this phenomenon have been observed (Ludwig et al. 2005;Shultzaberger et al. 2012).Whereas changes in cis-regulatory elements have been implicated in phenotypic and specifically morphological changes (Carroll 2008;Stern and Orgogozo 2008), other components of transcriptional regulation such as the chromatin environment have been scarcely explored (Lenhard et al. 2012). Histone modifications, which are chemical alterations of the histone spools upon which DNA is threaded, constitute one of the best-described elements of chromatin state (Zhou et al. 2011). These modifications can act directly or indirectly (through recruited enzymes) to alter DNA accessibility, thereby controlling other DNA-protein interactions (Campos and Reinberg 2009). Unlike TFBSs, however, histone modifications are not necessarily easily localizable to particular sequence elements, making their evolution difficult to study (Delest et al. 2012).Histone 3 lysine 27 trimethylation (H3K27me3) is one of the best-known histone modifications, in terms of both its biogenesis and effects. H3K27me3 is associated with complex cis-regulatory elements called Polycomb Response Elements (PREs) (Delest et al. 2012). Unlike TFBSs, PREs are compound regulatory elements composed of multiple, sometimes partially redundant, sequen...

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“…Epic/SICER performs normalization of data using a technique based on filtering with islands, as described in Zang et al. (2009), thus precluding the need for downsampling of lamin B1 ChIP‐Seq data (89 million reads in Young, 59 million reads in Old, Table S4). …”

Section: Methodsmentioning

confidence: 99%

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

et al. 2018

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SummaryIncreasing evidence suggests that regulation of heterochromatin at the nuclear envelope underlies metabolic disease susceptibility and age‐dependent metabolic changes, but the mechanism is unknown. Here, we profile lamina‐associated domains (LADs) using lamin B1 ChIP‐Seq in young and old hepatocytes and find that, although lamin B1 resides at a large fraction of domains at both ages, a third of lamin B1‐associated regions are bound exclusively at each age in vivo. Regions occupied by lamin B1 solely in young livers are enriched for the forkhead motif, bound by Foxa pioneer factors. We also show that Foxa2 binds more sites in Zmpste24 mutant mice, a progeroid laminopathy model, similar to increased Foxa2 occupancy in old livers. Aged and Zmpste24‐deficient livers share several features, including nuclear lamina abnormalities, increased Foxa2 binding, de‐repression of PPAR‐ and LXR‐dependent gene expression, and fatty liver. In old livers, additional Foxa2 binding is correlated to loss of lamin B1 and heterochromatin (H3K9me3 occupancy) at these loci. Our observations suggest that changes at the nuclear lamina are linked to altered Foxa2 binding, enabling opening of chromatin and de‐repression of genes encoding lipid synthesis and storage targets that contribute to etiology of hepatic steatosis.

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A clustering approach for identification of enriched domains from histone modification ChIP-Seq data

Abstract: Supplementary data are available at Bioinformatics online.

Cited by 964 publications

References 39 publications

Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status

Predictive properties of DNA methylation patterns in primary tumor samples for osteosarcoma relapse status

Evolution of H3K27me3-marked chromatin is linked to gene expression evolution and to patterns of gene duplication and diversification

Changes at the nuclear lamina alter binding of pioneer factor Foxa2 in aged liver

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