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

Thu-Hang Pham, and Benner, Christopher and Lichtinger, Monika and Schwarzfischer, Lucia and Hu, Yuhui and Andreesen, Reinhard and Chen, Wei and Rehli, Michael (2012) Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states. BLOOD, 119 (24). E161-E171. ISSN 0006-4971, 1528-0020

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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. (Blood. 2012;119(24):e161-e171)

Item Type: Article
Uncontrolled Keywords: SEQUENCE-BINDING-PROTEIN; GENE-EXPRESSION; MACROPHAGE DIFFERENTIATION; HISTONE MODIFICATIONS; CHROMATIN SIGNATURES; HUMAN GENOME; C/EBP-ALPHA; CELLS; PU.1; PROMOTER;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin III (Hämatologie und Internistische Onkologie)
Depositing User: Dr. Gernot Deinzer
Date Deposited: 11 May 2020 12:03
Last Modified: 11 May 2020 12:03
URI: https://pred.uni-regensburg.de/id/eprint/18581

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