title: Genome-wide ChIP-Seq reveals a dramatic shift in the binding of the transcription factor erythroid Kruppel-like factor during erythrocyte differentiation.
abstract: Erythropoiesis is dependent on the activity of transcription factors, including the erythroid-specific erythroid Kruppel-like factor (EKLF). ChIP followed by massively parallel sequencing (ChIP-Seq) is a powerful, unbiased method to map trans-factor occupancy. We used ChIP-Seq to study the interactome of EKLF in mouse erythroid progenitor cells and more differentiated erythroblasts. We correlated these results with the nuclear distribution of EKLF, RNA-Seq analysis of the transcriptome, and the occupancy of other erythroid transcription factors. In progenitor cells, EKLF is found predominantly at the periphery of the nucleus, where EKLF primarily occupies the promoter regions of genes and acts as a transcriptional activator. In erythroblasts, EKLF is distributed throughout the nucleus, and erythroblast-specific EKLF occupancy is predominantly in intragenic regions. In progenitor cells, EKLF modulates general cell growth and cell cycle regulatory pathways, whereas in erythroblasts EKLF is associated with repression of these pathways. The EKLF interactome shows very little overlap with the interactomes of GATA1, GATA2, or TAL1, leading to a model in which EKLF directs programs that are independent of those regulated by the GATA factors or TAL1.
authors: National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
authors: Andre M
authors: AM
authors: Pilon
authors: Subramanian S
authors: SS
authors: Ajay
authors: Swathi Ashok
authors: SA
authors: Kumar
authors: Laurie A
authors: LA
authors: Steiner
authors: Praveen F
authors: PF
authors: Cherukuri
authors: Stephen
authors: S
authors: Wincovitch
authors: Stacie M
authors: SM
authors: Anderson
authors: James C
authors: JC
authors: Mullikin
authors: Patrick G
authors: PG
authors: Gallagher
authors: Ross C
authors: RC
authors: Hardison
authors: Elliott H
authors: EH
authors: Margulies
authors: David M
authors: DM
authors: Bodine
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002874:Chromosome Mapping / Q000379:methods*; D004622:Embryo, Mammalian; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology*; D015672:Erythroid Precursor Cells / Q000378:metabolism / Q000502:physiology*; D004920:Erythropoiesis / Q000235:genetics / Q000502:physiology; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D011485:Protein Binding; D017422:Sequence Analysis, DNA / Q000379:methods; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C080774:erythroid Kruppel-like factor