Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data

被引：461

作者：

Pliner, Hannah A. ^{[1
]}

Packer, Jonathan S. ^{[1
]}

McFaline-Figueroa, Jose L. ^{[1
]}

Cusanovich, Darren A. ^{[1
]}

Daza, Riza M. ^{[1
]}

Aghamirzaie, Delasa ^{[1
]}

Srivatsan, Sanjay ^{[1
]}

Qiu, Xiaojie ^{[1
,2
]}

Jackson, Dana ^{[1
]}

Minkina, Anna ^{[1
]}

Adey, Andrew C. ^{[3
]}

Steemers, Frank J. ^{[4
]}

Shendure, Jay ^{[1
,5
,6
]}

Trapnell, Cole ^{[1
,6
]}

机构：

[1] Univ Washington, Dept Genome Sci, Seattle, WA 98195 USA

[2] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA

[3] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Portland, OR 97201 USA

[4] Illumina Inc, San Diego, CA USA

[5] Howard Hughes Med Inst, Seattle, WA 98195 USA

[6] Brotman Baty Inst Precis Med, Seattle, WA 98195 USA

来源：

MOLECULAR CELL | 2018年 / 71卷 / 05期

关键词：

GENE-EXPRESSION; READ ALIGNMENT; HUMAN GENOME; MYOD; BINDING; ACTIVATION; P300; TRANSPOSITION; ORGANIZATION; PROTEINS;

D O I：

10.1016/j.molcel.2018.06.044

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：

Linking regulatory DNA elements to their target genes, which may be located hundreds of kilobases away, remains challenging. Here, we introduce Cicero, an algorithm that identifies co-accessible pairs of DNA elements using single-cell chromatin accessibility data and so connects regulatory elements to their putative target genes. We apply Cicero to investigate how dynamically accessible elements orchestrate gene regulation in differentiating myoblasts. Groups of Cicero-linked regulatory elements meet criteria of "chromatin hubs"-they are enriched for physical proximity, interact with a common set of transcription factors, and undergo coordinated changes in histone marks that are predictive of changes in gene expression. Pseudotemporal analysis revealed that most DNA elements remain in chromatin hubs throughout differentiation. A subset of elements bound by MYOD1 in myoblasts exhibit early opening in a PBX1- and MEIS1-dependent manner. Our strategy can be applied to dissect the architecture, sequence determinants, and mechanisms of cis-regulation on a genome-wide scale.

引用

页码：858 / +

页数：22

共 62 条

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