Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules

Kelly, Theresa K.; Liu, Yaping; Lay, Fides D.; Liang, Gangning; Berman, Benjamin P.; Jones, Peter A.

doi:10.1101/gr.143008.112

Cited by 411 publications

(440 citation statements)

References 37 publications

(54 reference statements)

Supporting

Mentioning

398

Contrasting

Order By: Relevance

“…Another possibility is that at a subset of CEBPA-bound promoters, one allele is unmethylated and expressed whereas the other allele is methylated and repressed. This phenomenon has been observed for a small number of human promoters in a recent study (55).…”

Section: Model C: Reversal Of Methylation Upon Transcription Factor Bmentioning

confidence: 87%

Cross-talk between Site-specific Transcription Factors and DNA Methylation States

Blattler

Farnham

2013

Journal of Biological Chemistry

180

149

View full text Add to dashboard Cite

DNA methylation, which occurs predominantly at CpG dinucleotides, is a potent epigenetic repressor of transcription. Because DNA methylation is reversible, there is much interest in understanding the mechanisms by which it can be regulated by DNA-binding transcription factors. We discuss several models that, by incorporating sequence motifs, CpG density, and methylation levels, attempt to link the binding of a transcription factor with the acquisition or loss of DNA methylation at promoters and distal regulatory elements. Additional in vivo genome-wide characterization of transcription factor binding patterns and high-resolution DNA methylation analyses are clearly required for stronger support of each model. DNA methylation is a potent epigenetic repressor of transcription; promoters and enhancers that display high levels of methylation are essentially inactive (1, 2). Patterns of DNA methylation are tightly regulated in a tissue-specific manner, resulting in epigenetic specification of gene expression. Additionally, widespread genomic DNA hypomethylation in conjunction with local promoter-specific hypermethylation (which leads to inappropriate gene silencing) is centrally implicated in a myriad of human diseases from immunodeficiency-centromeric instability-facial anomalies syndrome to cancer (3-7). DNA methylation is potentially reversible (8), and there is much interest in understanding the mechanisms by which DNA methylation patterns are established. In this review, we focus on regulation of methylation patterns at mammalian genomic elements such as promoters and enhancers; for a summary of the regulation of large scale changes in methylation during development, we suggest a recent review by Smith and Meissner (9). It has been proposed that site-specific regulation of DNA methylation is mediated by DNA-binding transcription factors (TFs) 3 that interact with specific promoter or enhancer regions (10 -14). The functional relationship between DNA methylation and TF binding has been a subject of much interest for decades. Several models have been put forth that attempt to integrate the ability of a TF to bind to hyper-or hypo-methylated DNA with the acquisition and/or loss of DNA methylation at regulatory elements (Fig. 1). These include (a) protection from acquisition of DNA methylation upon binding of a TF to unmethylated DNA, (b) promotion of DNA methylation upon binding of a TF to unmethylated DNA, (c) reversal of DNA methylation upon binding of a TF to a region containing methylated DNA, and (d) reinforcement of repression upon binding of a TF to methylated DNA. In mammalian genomes, DNA methylation occurs predominantly at CpG dinucleotides. Regions of the genome are generally classified as those that have high CpG density (e.g. promoters) versus low CpG density (most of the genome). Additionally, the genome can be divided into categories based on CpG methylation levels: low methylation (promoters), intermediate methylation (distal regulatory elements), and high CpG methylation (most of the genome) (15)...

show abstract

Section: Model C: Reversal Of Methylation Upon Transcription Factor Bmentioning

confidence: 87%

Cross-talk between Site-specific Transcription Factors and DNA Methylation States

Blattler

Farnham

2013

Journal of Biological Chemistry

180

149

View full text Add to dashboard Cite

show abstract

“…Studies over the past two decades have shown that promoters having high levels of DNA methylation are not transcriptionally active [1][2][3]. Recent genome-wide epigenetic profiling efforts demonstrate that promoter regions with high levels of DNA methylation have low levels of active marks such as H3K4me3 and that methylated distal regulatory regions lack the active mark H3K27ac [4][5][6][7][8]. During neoplastic transformation, DNA methylation is reduced genomewide, but accumulates at certain promoters.…”

Section: Introductionmentioning

confidence: 99%

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

et al. 2014

View full text Add to dashboard Cite

Background: Gene expression is epigenetically regulated by a combination of histone modifications and methylation of CpG dinucleotides in promoters. In normal cells, CpG-rich promoters are typically unmethylated, marked with histone modifications such as H3K4me3, and are highly active. During neoplastic transformation, CpG dinucleotides of CG-rich promoters become aberrantly methylated, corresponding with the removal of active histone modifications and transcriptional silencing. Outside of promoter regions, distal enhancers play a major role in the cell type-specific regulation of gene expression. Enhancers, which function by bringing activating complexes to promoters through chromosomal looping, are also modulated by a combination of DNA methylation and histone modifications.

show abstract

“…Although ChIP-seq data delivers highly interpretable results, it is not well suited for 35 high-throughput studies due to high costs and laborious procedures. Thus, current large 36 epigenetic consortia such as Roadmap [39], Blueprint [1], and DEEP…”

mentioning

confidence: 99%

“…38 Instead, the generated epigenetic data is considered to predict TF binding, as it contains 39 a wealth of information to simplify this task. Especially data on open-chromatin, as 40 produced for example by DNaseI seq [34], ATAC-seq [6] or NOMe-seq [35], was shown 41 to be well tailored for this purpose [47] and has become the standard for the analysis of 42 tissue-specific TF binding in absence of TF-ChIP data. Using machine learning methods, 43 these predictions can be used to identify TFs acting as key regulators [4,46,47].…”

mentioning

confidence: 99%

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

Schmidt

Gasparoni

et al. 2016

Preprint

View full text Add to dashboard Cite

The binding and contribution of transcription factors (TF) to cell specific gene Using machine learning, we find low affinity binding sites to improve our ability to 10 explain gene expression variability compared to the standard presence/absence 11 classification of binding sites. Further, we show that both footprints and peaks capture 12 essential TF binding events and lead to a good prediction performance. In our nearly reach the quality of several TF ChIP-seq datasets. Finally, these scores correctly 15

show abstract

Genome-wide mapping of nucleosome positioning and DNA methylation within individual DNA molecules

Cited by 411 publications

References 37 publications

Cross-talk between Site-specific Transcription Factors and DNA Methylation States

Cross-talk between Site-specific Transcription Factors and DNA Methylation States

Global loss of DNA methylation uncovers intronic enhancers in genes showing expression changes

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

Contact Info

Product

Resources

About