Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

Ronan C. O'Malley, Shao-Shan Huang, Liang Song, Mathew G. Lewsey, Anna Bartlett, Joseph R. Nery, Mary Galli, Andrea Gallavotti, Joseph R. Ecker

Research output: Contribution to journalArticle

Abstract

The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-Throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75% (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism.

Original languageEnglish (US)
Pages (from-to)1280-1292
Number of pages13
JournalCell
Volume165
Issue number5
DOIs
StatePublished - May 19 2016

Fingerprint

DNA
Purification
Transcription Factors
Binding Sites
Arabidopsis
5-Methylcytosine
Methylation
Gene Regulatory Networks
Chemical modification
Complex networks
Throughput
Tissue
Costs and Cost Analysis
Growth
Costs

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

O'Malley, R. C., Huang, S-S., Song, L., Lewsey, M. G., Bartlett, A., Nery, J. R., ... Ecker, J. R. (2016). Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape. Cell, 165(5), 1280-1292. https://doi.org/10.1016/j.cell.2016.04.038

Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape. / O'Malley, Ronan C.; Huang, Shao-Shan; Song, Liang; Lewsey, Mathew G.; Bartlett, Anna; Nery, Joseph R.; Galli, Mary; Gallavotti, Andrea; Ecker, Joseph R.

In: Cell, Vol. 165, No. 5, 19.05.2016, p. 1280-1292.

Research output: Contribution to journalArticle

O'Malley, RC, Huang, S-S, Song, L, Lewsey, MG, Bartlett, A, Nery, JR, Galli, M, Gallavotti, A & Ecker, JR 2016, 'Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape', Cell, vol. 165, no. 5, pp. 1280-1292. https://doi.org/10.1016/j.cell.2016.04.038
O'Malley RC, Huang S-S, Song L, Lewsey MG, Bartlett A, Nery JR et al. Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape. Cell. 2016 May 19;165(5):1280-1292. https://doi.org/10.1016/j.cell.2016.04.038
O'Malley, Ronan C. ; Huang, Shao-Shan ; Song, Liang ; Lewsey, Mathew G. ; Bartlett, Anna ; Nery, Joseph R. ; Galli, Mary ; Gallavotti, Andrea ; Ecker, Joseph R. / Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape. In: Cell. 2016 ; Vol. 165, No. 5. pp. 1280-1292.
@article{c10c7beb818940769e80f9f9b56b5271,
title = "Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape",
abstract = "The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-Throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75{\%} (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism.",
author = "O'Malley, {Ronan C.} and Shao-Shan Huang and Liang Song and Lewsey, {Mathew G.} and Anna Bartlett and Nery, {Joseph R.} and Mary Galli and Andrea Gallavotti and Ecker, {Joseph R.}",
year = "2016",
month = "5",
day = "19",
doi = "10.1016/j.cell.2016.04.038",
language = "English (US)",
volume = "165",
pages = "1280--1292",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

AU - O'Malley, Ronan C.

AU - Huang, Shao-Shan

AU - Song, Liang

AU - Lewsey, Mathew G.

AU - Bartlett, Anna

AU - Nery, Joseph R.

AU - Galli, Mary

AU - Gallavotti, Andrea

AU - Ecker, Joseph R.

PY - 2016/5/19

Y1 - 2016/5/19

N2 - The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-Throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75% (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism.

AB - The cistrome is the complete set of transcription factor (TF) binding sites (cis-elements) in an organism, while an epicistrome incorporates tissue-specific DNA chemical modifications and TF-specific chemical sensitivities into these binding profiles. Robust methods to construct comprehensive cistrome and epicistrome maps are critical for elucidating complex transcriptional networks that underlie growth, behavior, and disease. Here, we describe DNA affinity purification sequencing (DAP-seq), a high-Throughput TF binding site discovery method that interrogates genomic DNA with in-vitro-expressed TFs. Using DAP-seq, we defined the Arabidopsis cistrome by resolving motifs and peaks for 529 TFs. Because genomic DNA used in DAP-seq retains 5-methylcytosines, we determined that >75% (248/327) of Arabidopsis TFs surveyed were methylation sensitive, a property that strongly impacts the epicistrome landscape. DAP-seq datasets also yielded insight into the biology and binding site architecture of numerous TFs, demonstrating the value of DAP-seq for cost-effective cistromic and epicistromic annotation in any organism.

UR - http://www.scopus.com/inward/record.url?scp=84975134214&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975134214&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2016.04.038

DO - 10.1016/j.cell.2016.04.038

M3 - Article

VL - 165

SP - 1280

EP - 1292

JO - Cell

JF - Cell

SN - 0092-8674

IS - 5

ER -