Cistrome and Epicistrome Features Shape the Regulatory DNA Landscape

Ronan C. O'Malley, Shao Shan Carol 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

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

O'Malley, R. C., Huang, S. S. C., Song, L., Lewsey, M. G., Bartlett, A., Nery, J. R., Galli, M., Gallavotti, A., & 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