NDLI: Identification of biologically relevant enhancers in human erythroid cells.

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Identification of biologically relevant enhancers in human erythroid cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Steiner, Laurie A. Schulz, Vincent P. Hardison, Ross C. Bogardus, Hannah Mishra, Tejaswini Su, Mack Y. Gallagher, Patrick G.
Description	Author Affiliation: Su MY ( Department of Pediatrics, Yale University School of Medicine, New Haven, Connecticut 06520, USA.)
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. We hypothesized 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.
ISSN	00219258
e-ISSN	1083351X
Journal	Journal of Biological Chemistry
Issue Number	12
Volume Number	288
Language	English
Publisher	American Society for Biochemistry and Molecular Biology (United States)
Publisher Date	2013-03-22
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Enhancer Elements, Genetic Erythroid Cells Metabolism Gene Expression Regulation Basic Helix-Loop-Helix Transcription Factors Physiology Cells, Cultured Chromatin Genetics Chromatin Immunoprecipitation Conserved Sequence E1A-Associated P300 Protein GATA1 Transcription Factor Genes, Reporter High-Throughput Nucleotide Sequencing Kruppel-Like Transcription Factors Luciferases, Firefly Biosynthesis Molecular Sequence Annotation NF-E2 Transcription Factor, P45 Subunit Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide Promoter Regions, Genetic Protein Binding Proto-Oncogene Proteins RNA, Messenger Sequence Analysis, DNA Transcriptome Research Support, N.I.H., Intramural Biochemistry Molecular Biology
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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