scholarly journals The Binding Sites for the Chromatin Insulator Protein CTCF Map to DNA Methylation-Free Domains Genome-Wide

2004 ◽  
Vol 14 (8) ◽  
pp. 1594-1602 ◽  
Author(s):  
R. Mukhopadhyay
2018 ◽  
Author(s):  
R Spektor ◽  
ND Tippens ◽  
CA Mimoso ◽  
PD Soloway

ABSTRACTChromatin features are characterized by genome-wide assays for nucleosome location, protein binding sites, 3-dimensional interactions, and modifications to histones and DNA. For example, Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) identifies nucleosome-depleted (open) chromatin, which harbors potentially active gene regulatory sequences; and bisulfite sequencing (BS-seq) quantifies DNA methylation. When two distinct chromatin features like these are assayed separately in populations of cells, it is impossible to determine, with certainty, where the features are coincident in the genome by simply overlaying datasets. Here we describe methyl-ATAC-seq (mATAC-seq), which implements modifications to ATAC-seq, including subjecting the output to BS-seq. Merging these assays into a single protocol identifies the locations of open chromatin, and reveals, unambiguously, the DNA methylation state of the underlying DNA. Such combinatorial methods eliminate the need to perform assays independently and infer where features are coincident.


2013 ◽  
Author(s):  
Benjamin P. Berman ◽  
Yaping Liu ◽  
Theresa K. Kelly

Nucleosome organization and DNA methylation are two epigenetic mechanisms that are important for proper control of mammalian transcription. Numerous lines of evidence suggest an interaction between these two mechanisms, but the nature of this interaction in vivo remains elusive. Whole-genome DNA methylation sequencing studies have shown that human methylation levels are periodic at intervals of approximately 190 bp, suggesting a genome-wide relationship between the two marks. A recent report (Chodavarapu et al., 2010) attributed this to higher methylation levels of DNA within nucleosomes. Here, we propose an alternate explanation for these nucleosomal periodicities. By examining methylation patterns in published datasets, we find that genome-wide methylation levels are highest within the linker regions that occur between nucleosomes in multi-nucleosome arrays. This effect is most prominent within long-range Partially Methylated Domains (PMDs) and the strongly positioned nucleosomes that flank CTCF binding sites. The CTCF-flanking nucleosomes retain positioning even in regions completely devoid of CpG dinucleotides, suggesting that DNA methylation is not required for proper positioning. We propose that DNA methylation is inhibited by histone proteins at CTCF and other unknown classes of nucleosomes within PMDs.


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