Identification of biologically relevant enhancers in human erythroid cells

MacK Y. Su, Laurie A. Steiner, Hannah Bogardus, Tejaswini Mishra, Vincent P. Schulz, Ross Cameron Hardison, Patrick G. Gallagher

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

Identification of cell type-specific enhancers is important for understanding the regulation of programs controlling cellular development and differentiation. Enhancers are typically marked by the co-transcriptional activator protein p300 or by groups of cell-expressed transcription factors.Wehypothesized that a unique set of enhancers regulates gene expression in human erythroid cells, a highly specialized cell type evolved to provide adequate amounts of oxygen throughout the body. Using chromatin immunoprecipitation followed by massively parallel sequencing, genome-wide maps of candidate enhancers were constructed for p300 and four transcription factors, GATA1, NF-E2, KLF1, and SCL, using primary human erythroid cells. These data were combined with gene expression analyses, and candidate enhancers were identified. Consistent with their predicted function as candidate enhancers, there was statistically significant enrichment of p300 and combinations of co-localizing erythroid transcription factors within 1-50 kb of the transcriptional start site (TSS) of genes highly expressed in erythroid cells. Candidate enhancers were also enriched near genes with known erythroid cell function or phenotype. Candidate enhancers exhibited moderate conservation with mouse and minimal conservation with nonplacental vertebrates. Candidate enhancers were mapped to a set of erythroid-associated, biologically relevant, SNPs from the genome-wide association studies (GWAS) catalogue of NHGRI, National Institutes of Health. Fourteen candidate enhancers, representing 10 genetic loci, mapped to sites associated with biologically relevant erythroid traits. Fragments from these loci directed statistically significant expression in reporter gene assays. Identification of enhancers in human erythroid cells will allow a better understanding of erythroid cell development, differentiation, structure, and function and provide insights into inherited and acquired hematologic disease.

Original languageEnglish (US)
Pages (from-to)8433-8444
Number of pages12
JournalJournal of Biological Chemistry
Volume288
Issue number12
DOIs
StatePublished - Mar 22 2013

Fingerprint

Erythroid Cells
Genes
GATA1 Transcription Factor
Gene expression
Conservation
Transcription Factors
National Human Genome Research Institute (U.S.)
NF-E2 Transcription Factor
Gene Expression
High-Throughput Nucleotide Sequencing
Genetic Loci
Hematologic Diseases
Chromatin Immunoprecipitation
Genome-Wide Association Study
National Institutes of Health (U.S.)
Chromatin
Assays
Reporter Genes
Single Nucleotide Polymorphism
Vertebrates

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Su, M. Y., Steiner, L. A., Bogardus, H., Mishra, T., Schulz, V. P., Hardison, R. C., & Gallagher, P. G. (2013). Identification of biologically relevant enhancers in human erythroid cells. Journal of Biological Chemistry, 288(12), 8433-8444. https://doi.org/10.1074/jbc.M112.413260
Su, MacK Y. ; Steiner, Laurie A. ; Bogardus, Hannah ; Mishra, Tejaswini ; Schulz, Vincent P. ; Hardison, Ross Cameron ; Gallagher, Patrick G. / Identification of biologically relevant enhancers in human erythroid cells. In: Journal of Biological Chemistry. 2013 ; Vol. 288, No. 12. pp. 8433-8444.
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Su, MY, Steiner, LA, Bogardus, H, Mishra, T, Schulz, VP, Hardison, RC & Gallagher, PG 2013, 'Identification of biologically relevant enhancers in human erythroid cells', Journal of Biological Chemistry, vol. 288, no. 12, pp. 8433-8444. https://doi.org/10.1074/jbc.M112.413260

Identification of biologically relevant enhancers in human erythroid cells. / Su, MacK Y.; Steiner, Laurie A.; Bogardus, Hannah; Mishra, Tejaswini; Schulz, Vincent P.; Hardison, Ross Cameron; Gallagher, Patrick G.

In: Journal of Biological Chemistry, Vol. 288, No. 12, 22.03.2013, p. 8433-8444.

Research output: Contribution to journalArticle

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AU - Hardison, Ross Cameron

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