ATAC-Me Captures Prolonged DNA Methylation of Dynamic Chromatin Accessibility Loci during Cell Fate Transitions

被引：54

作者：

Barnett, Kelly R. ^{[1
,2
]}

Decato, Benjamin E. ^{[3
]}

Scott, Timothy J. ^{[1
,2
]}

Hansen, Tyler J. ^{[1
,2
]}

Chen, Bob ^{[1
,2
]}

Attalla, Jonathan ^{[1
,2
]}

Smith, Andrew D. ^{[3
]}

Hodges, Emily ^{[1
,2
]}

机构：

[1] Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Sch Med, Vanderbilt Genet Inst, Nashville, TN 37232 USA

[3] Univ Southern Calif, Dept Biol Sci, Quantitat & Computat Biol, Los Angeles, CA 90089 USA

来源：

MOLECULAR CELL | 2020年 / 77卷 / 06期

基金：

美国国家卫生研究院;

关键词：

READ ALIGNMENT; DIFFERENTIATION; TRANSCRIPTION; GENE; LANDSCAPE; ENHANCERS; DEMETHYLATION; ANNOTATION; MACROPHAGE; EXPRESSION;

D O I：

10.1016/j.molcel.2020.01.004

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

DNA methylation of enhancers is dynamic, cell-type specific, and vital for cell fate progression. However, current models inadequately define its role within the hierarchy of gene regulation. Analysis of independent datasets shows an unanticipated overlap between DNA methylation and chromatin accessibility at enhancers of steady-state stem cells, suggesting that these two opposing features might exist concurrently. To define their temporal relationship, we developed ATAC-Me, which probes accessibility and methylation from single DNA library preparations. We identified waves of accessibility occurring rapidly across thousands of myeloid enhancers in a monocyte-to-macrophage cell fate model. Prolonged methylation states were observed at a majority of these sites, while transcription of nearby genes tracked closely with accessibility. ATAC-Me uncovers a significant disconnect between chromatin accessibility, DNA methylation status, and gene activity. This unexpected observation highlights the value of ATAC-Me in constructing precise molecular timelines for understanding the role of DNA methylation in gene regulation.

引用

页码：1350 / +

页数：21

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