Molecular Pathology, University of Tartu, Tartu, Estonia.
BMC Genomics. 2010 Nov 18;11:642. doi: 10.1186/1471-2164-11-642.
Monocyte-derived macrophages and dendritic cells (DCs) are important in inflammatory processes and are often used for immunotherapeutic approaches. Blood monocytes can be differentiated into macrophages and DCs, which is accompanied with transcriptional changes in many genes, including chemokines and cell surface markers.
To study the chromatin modifications associated with this differentiation, we performed a genome wide analysis of histone H3 trimethylation on lysine 4 (H3K4me3) and 27 (H3K27me3) as well as acetylation of H3 lysines (AcH3) in promoter regions. We report that both H3K4me3 and AcH3 marks significantly correlate with transcriptionally active genes whereas H3K27me3 mark is associated with inactive gene promoters. During differentiation, the H3K4me3 levels decreased on monocyte-specific CD14, CCR2 and CX3CR1 but increased on DC-specific TM7SF4/DC-STAMP, TREM2 and CD209/DC-SIGN genes. Genes associated with phagocytosis and antigen presentation were marked by H3K4me3 modifications. We also report that H3K4me3 levels on clustered chemokine and surface marker genes often correlate with transcriptional activity.
Our results provide a basis for further functional correlations between gene expression and histone modifications in monocyte-derived macrophages and DCs.
单核细胞衍生的巨噬细胞和树突状细胞（DC）在炎症过程中很重要，常用于免疫治疗方法。血液中的单核细胞可以分化为巨噬细胞和 DC，这伴随着许多基因的转录变化，包括趋化因子和细胞表面标记物。
为了研究与这种分化相关的染色质修饰，我们对组蛋白 H3 赖氨酸 4（H3K4me3）和 27（H3K27me3）的三甲基化以及启动子区域的 H3 赖氨酸乙酰化进行了全基因组分析。我们报告说，H3K4me3 和 AcH3 标记与转录活性基因显著相关，而 H3K27me3 标记与非活性基因启动子相关。在分化过程中，单核细胞特异性 CD14、CCR2 和 CX3CR1 的 H3K4me3 水平降低，但 DC 特异性 TM7SF4/DC-STAMP、TREM2 和 CD209/DC-SIGN 基因的 H3K4me3 水平增加。与吞噬作用和抗原呈递相关的基因被 H3K4me3 修饰标记。我们还报告说，趋化因子和表面标记基因簇的 H3K4me3 水平通常与转录活性相关。
我们的结果为单核细胞衍生的巨噬细胞和 DC 中基因表达与组蛋白修饰之间的进一步功能相关性提供了基础。
