Department of Hematology, University Hospital Regensburg, Regensburg, Germany.
Blood. 2012 Jun 14;119(24):e161-71. doi: 10.1182/blood-2012-01-402453. Epub 2012 May 1.
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.
细胞分化是由谱系特异性转录因子协调的，并与细胞类型特异性表观遗传特征相关。在本研究中，我们使用阶段特异性的、表观遗传的“指纹”来推断人类单核细胞分化过程中的关键转录调节因子。我们全局绘制了表观遗传增强子标记（组蛋白 H3 赖氨酸 4 单甲基化、组蛋白 H3 赖氨酸 27 乙酰化和组蛋白变体 H2AZ）的分布，描述了标记区域的一般性质，并表明细胞类型特异性的表观遗传“指纹”与所有研究的分化阶段（即造血干细胞、单核细胞和巨噬细胞）的特定、从头衍生的 motif 特征相关。我们通过 ChIP 测序验证了新的、从头衍生的巨噬细胞特异性增强子特征，该特征包括 ETS、CEBP、bZIP、EGR、E-Box 和 NF-κB 基序，证实了它们与分化相关的表观遗传变化有关。我们在此描述了人类巨噬细胞分化的动态增强子景观，强调了全基因组表观遗传谱研究揭示新的功能见解的力量，并为巨噬细胞生物学家提供了独特的资源。
