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

Hannah A. Pliner, Jonathan S. Packer, José L. McFaline-Figueroa, Darren A. Cusanovich, Riza M. Daza, Delasa Aghamirzaie, Sanjay Srivatsan, Xiaojie Qiu, Dana Jackson, Anna Minkina, Andrew Adey, Frank J. Steemers, Jay Shendure, Cole Trapnell

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

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. Pliner et al. introduce Cicero, a software program to connect distal regulatory elements with target genes using single-cell ATAC-seq data. They find evidence that groups of co-accessible elements form chromatin hubs and undergo coordinated changes in histone marks that are predictive of changes in gene expression in skeletal muscle development.

Original languageEnglish (US)
Pages (from-to)858-871.e8
JournalMolecular Cell
Volume71
Issue number5
DOIs
StatePublished - Sep 6 2018

Fingerprint

Cell Communication
Chromatin
Histone Code
Myoblasts
DNA
Genes
Gene Expression
Muscle Development
Skeletal Muscle
Transcription Factors
Software
Genome

Keywords

  • ATAC-seq
  • chromatin accessibility
  • co-accessibility
  • gene regulation
  • machine learning
  • myoblast differentiation
  • single-cell

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Pliner, H. A., Packer, J. S., McFaline-Figueroa, J. L., Cusanovich, D. A., Daza, R. M., Aghamirzaie, D., ... Trapnell, C. (2018). Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data. Molecular Cell, 71(5), 858-871.e8. https://doi.org/10.1016/j.molcel.2018.06.044

Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data. / Pliner, Hannah A.; Packer, Jonathan S.; McFaline-Figueroa, José L.; Cusanovich, Darren A.; Daza, Riza M.; Aghamirzaie, Delasa; Srivatsan, Sanjay; Qiu, Xiaojie; Jackson, Dana; Minkina, Anna; Adey, Andrew; Steemers, Frank J.; Shendure, Jay; Trapnell, Cole.

In: Molecular Cell, Vol. 71, No. 5, 06.09.2018, p. 858-871.e8.

Research output: Contribution to journalArticle

Pliner, HA, Packer, JS, McFaline-Figueroa, JL, Cusanovich, DA, Daza, RM, Aghamirzaie, D, Srivatsan, S, Qiu, X, Jackson, D, Minkina, A, Adey, A, Steemers, FJ, Shendure, J & Trapnell, C 2018, 'Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data', Molecular Cell, vol. 71, no. 5, pp. 858-871.e8. https://doi.org/10.1016/j.molcel.2018.06.044
Pliner HA, Packer JS, McFaline-Figueroa JL, Cusanovich DA, Daza RM, Aghamirzaie D et al. Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data. Molecular Cell. 2018 Sep 6;71(5):858-871.e8. https://doi.org/10.1016/j.molcel.2018.06.044
Pliner, Hannah A. ; Packer, Jonathan S. ; McFaline-Figueroa, José L. ; Cusanovich, Darren A. ; Daza, Riza M. ; Aghamirzaie, Delasa ; Srivatsan, Sanjay ; Qiu, Xiaojie ; Jackson, Dana ; Minkina, Anna ; Adey, Andrew ; Steemers, Frank J. ; Shendure, Jay ; Trapnell, Cole. / Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data. In: Molecular Cell. 2018 ; Vol. 71, No. 5. pp. 858-871.e8.
@article{a8119deeb9584179aa2d2bd2e6e4c13d,
title = "Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data",
abstract = "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. Pliner et al. introduce Cicero, a software program to connect distal regulatory elements with target genes using single-cell ATAC-seq data. They find evidence that groups of co-accessible elements form chromatin hubs and undergo coordinated changes in histone marks that are predictive of changes in gene expression in skeletal muscle development.",
keywords = "ATAC-seq, chromatin accessibility, co-accessibility, gene regulation, machine learning, myoblast differentiation, single-cell",
author = "Pliner, {Hannah A.} and Packer, {Jonathan S.} and McFaline-Figueroa, {Jos{\'e} L.} and Cusanovich, {Darren A.} and Daza, {Riza M.} and Delasa Aghamirzaie and Sanjay Srivatsan and Xiaojie Qiu and Dana Jackson and Anna Minkina and Andrew Adey and Steemers, {Frank J.} and Jay Shendure and Cole Trapnell",
year = "2018",
month = "9",
day = "6",
doi = "10.1016/j.molcel.2018.06.044",
language = "English (US)",
volume = "71",
pages = "858--871.e8",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Cicero Predicts cis-Regulatory DNA Interactions from Single-Cell Chromatin Accessibility Data

AU - Pliner, Hannah A.

AU - Packer, Jonathan S.

AU - McFaline-Figueroa, José L.

AU - Cusanovich, Darren A.

AU - Daza, Riza M.

AU - Aghamirzaie, Delasa

AU - Srivatsan, Sanjay

AU - Qiu, Xiaojie

AU - Jackson, Dana

AU - Minkina, Anna

AU - Adey, Andrew

AU - Steemers, Frank J.

AU - Shendure, Jay

AU - Trapnell, Cole

PY - 2018/9/6

Y1 - 2018/9/6

N2 - 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. Pliner et al. introduce Cicero, a software program to connect distal regulatory elements with target genes using single-cell ATAC-seq data. They find evidence that groups of co-accessible elements form chromatin hubs and undergo coordinated changes in histone marks that are predictive of changes in gene expression in skeletal muscle development.

AB - 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. Pliner et al. introduce Cicero, a software program to connect distal regulatory elements with target genes using single-cell ATAC-seq data. They find evidence that groups of co-accessible elements form chromatin hubs and undergo coordinated changes in histone marks that are predictive of changes in gene expression in skeletal muscle development.

KW - ATAC-seq

KW - chromatin accessibility

KW - co-accessibility

KW - gene regulation

KW - machine learning

KW - myoblast differentiation

KW - single-cell

UR - http://www.scopus.com/inward/record.url?scp=85053831649&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85053831649&partnerID=8YFLogxK

U2 - 10.1016/j.molcel.2018.06.044

DO - 10.1016/j.molcel.2018.06.044

M3 - Article

VL - 71

SP - 858-871.e8

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 5

ER -