title: Hematopoietic transcriptional mechanisms: from locus-specific to genome-wide vantage points.
abstract: Hematopoiesis is an exquisitely regulated process in which stem cells in the developing embryo and the adult generate progenitor cells that give rise to all blood lineages. Master regulatory transcription factors control hematopoiesis by integrating signals from the microenvironment and dynamically establishing and maintaining genetic networks. One of the most rudimentary aspects of cell type-specific transcription factor function, how they occupy a highly restricted cohort of cis-elements in chromatin, remains poorly understood. Transformative technologic advances involving the coupling of next-generation DNA sequencing technology with the chromatin immunoprecipitation assay (ChIP-seq) have enabled genome-wide mapping of factor occupancy patterns. However, formidable problems remain; notably, ChIP-seq analysis yields hundreds to thousands of chromatin sites occupied by a given transcription factor, and only a fraction of the sites appear to be endowed with critical, non-redundant function. It has become en vogue to map transcription factor occupancy patterns genome-wide, while using powerful statistical tools to establish correlations to inform biology and mechanisms. With the advent of revolutionary genome editing technologies, one can now reach beyond correlations to conduct definitive hypothesis testing. This review focuses on key discoveries that have emerged during the path from single loci to genome-wide analyses, specifically in the context of hematopoietic transcriptional mechanisms.
authors.affiliation: Carbone Cancer Center, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; University of Wisconsin-Madison Blood Research Program, Madison, Wisconsin, USA.
authors.forename: Andrew W
authors.initials: AW
authors.lastname: DeVilbiss
authors.affiliation: Carbone Cancer Center, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; University of Wisconsin-Madison Blood Research Program, Madison, Wisconsin, USA.
authors.forename: Rajendran
authors.initials: R
authors.lastname: Sanalkumar
authors.affiliation: Carbone Cancer Center, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; University of Wisconsin-Madison Blood Research Program, Madison, Wisconsin, USA.
authors.forename: Kirby D
authors.initials: KD
authors.lastname: Johnson
authors.affiliation: University of Wisconsin-Madison Blood Research Program, Madison, Wisconsin, USA; Department of Biostatistics and Medical Informatics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
authors.forename: Sunduz
authors.initials: S
authors.lastname: Keles
authors.affiliation: Carbone Cancer Center, Department of Cell and Regenerative Biology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA; University of Wisconsin-Madison Blood Research Program, Madison, Wisconsin, USA. Electronic address: ehbresni@wisc.edu.
authors.forename: Emery H
authors.initials: EH
authors.lastname: Bresnick
mesh_terms: D047369:Chromatin Immunoprecipitation; D050982:GATA1 Transcription Factor / Q000502:physiology; D055106:Genome-Wide Association Study; D006410:Hematopoiesis; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000502:physiology; D017422:Sequence Analysis, DNA; D014158:Transcription, Genetic
chemical_list: D050982:GATA1 Transcription Factor; C494688:GATA1 protein, human; D051741:Kruppel-Like Transcription Factors; C080774:erythroid Kruppel-like factor