title: Dynamic epigenetic enhancer signatures reveal key transcription factors associated with monocytic differentiation states.
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-κB motifs, by ChIP sequencing for a subset of motif corresponding transcription factors (PU.1, C/EBPβ, 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.
authors.affiliation: Department of Hematology, University Hospital Regensburg, Regensburg, Germany.
authors.forename: Thu-Hang
authors.initials: TH
authors.lastname: Pham
authors.forename: Christopher
authors.initials: C
authors.lastname: Benner
authors.forename: Monika
authors.initials: M
authors.lastname: Lichtinger
authors.forename: Lucia
authors.initials: L
authors.lastname: Schwarzfischer
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Hu
authors.forename: Reinhard
authors.initials: R
authors.lastname: Andreesen
authors.forename: Wei
authors.initials: W
authors.lastname: Chen
authors.forename: Michael
authors.initials: M
authors.lastname: Rehli
mesh_terms: D000107:Acetylation; D001483:Base Sequence; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics*; D004194:Disease / Q000235:genetics; D051767:Early Growth Response Protein 2 / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic; D014644:Genetic Variation; D006657:Histones / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000166:cytology / Q000378:metabolism; D008745:Methylation; D008954:Models, Biological; D008969:Molecular Sequence Data; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism*; D059372:Nucleotide Motifs / Q000235:genetics; D009928:Organ Specificity / Q000235:genetics; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D051767:Early Growth Response Protein 2; D006657:Histones; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099232:Proto-Oncogene Protein Spi-1; C497326:EGR2 protein, human