1. Large DNA Methylation Nadirs Anchor Chromatin Loops Maintaining Hematopoietic Stem Cell Identity.
- Author
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Zhang X, Jeong M, Huang X, Wang XQ, Wang X, Zhou W, Shamim MS, Gore H, Himadewi P, Liu Y, Bochkov ID, Reyes J, Doty M, Huang YH, Jung H, Heikamp E, Aiden AP, Li W, Su J, Aiden EL, and Goodell MA
- Subjects
- CCCTC-Binding Factor genetics, CCCTC-Binding Factor metabolism, Cell Differentiation, Chromatin metabolism, Enhancer of Zeste Homolog 2 Protein genetics, Enhancer of Zeste Homolog 2 Protein metabolism, Epigenesis, Genetic, Gene Expression Regulation, Histones genetics, Histones metabolism, Homeodomain Proteins genetics, Humans, In Situ Hybridization, Fluorescence, Lysine genetics, Lysine metabolism, Nuclear Proteins genetics, SOXB1 Transcription Factors genetics, Short Stature Homeobox Protein genetics, Transcription Factors genetics, Chromatin chemistry, Chromatin genetics, DNA Methylation, Hematopoietic Stem Cells cytology, Hematopoietic Stem Cells physiology
- Abstract
Higher-order chromatin structure and DNA methylation are implicated in multiple developmental processes, but their relationship to cell state is unknown. Here, we find that large (>7.3 kb) DNA methylation nadirs (termed "grand canyons") can form long loops connecting anchor loci that may be dozens of megabases (Mb) apart, as well as inter-chromosomal links. The interacting loci cover a total of ∼3.5 Mb of the human genome. The strongest interactions are associated with repressive marks made by the Polycomb complex and are diminished upon EZH2 inhibitor treatment. The data are suggestive of the formation of these loops by interactions between repressive elements in the loci, forming a genomic subcompartment, rather than by cohesion/CTCF-mediated extrusion. Interestingly, unlike previously characterized subcompartments, these interactions are present only in particular cell types, such as stem and progenitor cells. Our work reveals that H3K27me3-marked large DNA methylation grand canyons represent a set of very-long-range loops associated with cellular identity., Competing Interests: Declaration of Interests The authors declare no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)
- Published
- 2020
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