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Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states

Item Type:Article
Title:Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states
Creators Name:Pham, T.H. and Benner, C. and Lichtinger, M. and Schwarzfischer, L. and Hu, Y. and Andreesen, R. and Chen, W. and Rehli, M.
Abstract:Cellular differentiation is orchestrated by lineage-specific transcription factors and associated with cell type-specific epigenetic signatures. In the present study, we used stage-specific, epigenetic "fingerprints" to deduce key transcriptional regulators of the human monocytic differentiation process. We globally mapped the distribution of epigenetic enhancer marks (histone H3 lysine 4 monomethylation, histone H3 lysine 27 acetylation, and the histone variant H2AZ), describe general properties of marked regions, and show that cell type-specific epigenetic "fingerprints" are correlated with specific, de novo-derived motif signatures at all of the differentiation stages studied (ie, hematopoietic stem cells, monocytes, and macrophages). We validated the novel, de novo-derived, macrophage-specific enhancer signature, which included ETS, CEBP, bZIP, EGR, E-Box and NF-{kappa}B motifs, by ChIP sequencing for a subset of motif corresponding transcription factors (PU.1, C/EBP{beta}, and EGR2), confirming their association with differentiation-associated epigenetic changes. We describe herein the dynamic enhancer landscape of human macrophage differentiation, highlight the power of genome-wide epigenetic profiling studies to reveal novel functional insights, and provide a unique resource for macrophage biologists.
Keywords:Acetylation, Base Sequence, Biological Models, CCAAT-Enhancer-Binding Protein-beta, Cell Differentiation, Disease, Early Growth Response Protein 2, Genetic Enhancer Elements, Genetic Epigenesis, Genetic Variation, Histones, Macrophages, Methylation, Molecular Sequence Data, Monocytes, Nucleotide Motifs, Organ Specificity, Protein Binding, Proto-Oncogene Proteins, Trans-Activators, Transcription Factors
Publisher:American Society of Hematology
Page Range:e161-e171
Date:14 June 2012
Official Publication:https://doi.org/10.1182/blood-2012-01-402453
PubMed:View item in PubMed

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