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Predicting cell-type-specific gene expression from regions of open chromatin.

Publication ,  Journal Article
Natarajan, A; Yardimci, GG; Sheffield, NC; Crawford, GE; Ohler, U
Published in: Genome Res
September 2012

Complex patterns of cell-type-specific gene expression are thought to be achieved by combinatorial binding of transcription factors (TFs) to sequence elements in regulatory regions. Predicting cell-type-specific expression in mammals has been hindered by the oftentimes unknown location of distal regulatory regions. To alleviate this bottleneck, we used DNase-seq data from 19 diverse human cell types to identify proximal and distal regulatory elements at genome-wide scale. Matched expression data allowed us to separate genes into classes of cell-type-specific up-regulated, down-regulated, and constitutively expressed genes. CG dinucleotide content and DNA accessibility in the promoters of these three classes of genes displayed substantial differences, highlighting the importance of including these aspects in modeling gene expression. We associated DNase I hypersensitive sites (DHSs) with genes, and trained classifiers for different expression patterns. TF sequence motif matches in DHSs provided a strong performance improvement in predicting gene expression over the typical baseline approach of using proximal promoter sequences. In particular, we achieved competitive performance when discriminating up-regulated genes from different cell types or genes up- and down-regulated under the same conditions. We identified previously known and new candidate cell-type-specific regulators. The models generated testable predictions of activating or repressive functions of regulators. DNase I footprints for these regulators were indicative of their direct binding to DNA. In summary, we successfully used information of open chromatin obtained by a single assay, DNase-seq, to address the problem of predicting cell-type-specific gene expression in mammalian organisms directly from regulatory sequence.

Duke Scholars

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Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

September 2012

Volume

22

Issue

9

Start / End Page

1711 / 1722

Location

United States

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Protein Binding
  • Promoter Regions, Genetic
  • Organ Specificity
  • Humans
  • Genome
  • Gene Expression Regulation
  • Gene Expression Profiling
 

Citation

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Natarajan, A., Yardimci, G. G., Sheffield, N. C., Crawford, G. E., & Ohler, U. (2012). Predicting cell-type-specific gene expression from regions of open chromatin. Genome Res, 22(9), 1711–1722. https://doi.org/10.1101/gr.135129.111
Natarajan, Anirudh, Galip Gürkan Yardimci, Nathan C. Sheffield, Gregory E. Crawford, and Uwe Ohler. “Predicting cell-type-specific gene expression from regions of open chromatin.Genome Res 22, no. 9 (September 2012): 1711–22. https://doi.org/10.1101/gr.135129.111.
Natarajan A, Yardimci GG, Sheffield NC, Crawford GE, Ohler U. Predicting cell-type-specific gene expression from regions of open chromatin. Genome Res. 2012 Sep;22(9):1711–22.
Natarajan, Anirudh, et al. “Predicting cell-type-specific gene expression from regions of open chromatin.Genome Res, vol. 22, no. 9, Sept. 2012, pp. 1711–22. Pubmed, doi:10.1101/gr.135129.111.
Natarajan A, Yardimci GG, Sheffield NC, Crawford GE, Ohler U. Predicting cell-type-specific gene expression from regions of open chromatin. Genome Res. 2012 Sep;22(9):1711–1722.

Published In

Genome Res

DOI

EISSN

1549-5469

Publication Date

September 2012

Volume

22

Issue

9

Start / End Page

1711 / 1722

Location

United States

Related Subject Headings

  • Transcription Initiation Site
  • Transcription Factors
  • Regulatory Sequences, Nucleic Acid
  • Protein Binding
  • Promoter Regions, Genetic
  • Organ Specificity
  • Humans
  • Genome
  • Gene Expression Regulation
  • Gene Expression Profiling