Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T helper 1 and T helper 2 Cell Polarization
Global Chromatin State Analysis Reveals Lineage-Specific Enhancers during the Initiation of Human T helper 1 and T helper 2 Cell Polarization
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DOI：
10.1016/j.immuni.2013.05.011
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发表时间：
2013-06-27
期刊：
影响因子：
32.4
通讯作者：
Lahesmaa, Riitta
中科院分区：
文献类型：
--
作者：
Hawkins, R. David;Larjo, Antti;Lahesmaa, Riitta
幼稚CD4（+）T细胞可以分化成特定的辅助和调节T细胞谱系，以对抗感染和疾病。对细胞因子的正确反应和这些群体的受控平衡对于免疫系统和避免自身免疫性疾病至关重要。为了研究早期细胞命运承诺是如何调节的，我们生成了第一个人类全基因组蛋白修饰图，该图揭示了体外极化72小时后向辅助性T细胞1（Th1）和辅助性T细胞2（Th2）细胞谱系的增强子元件。我们的分析表明，即使在这个非常早期的时间点，细胞特异性基因调控和增强子也在指导谱系定型。对谱系特异性增强子的进一步检查鉴定了具有已知和未知T细胞作用的转录因子（TF）作为谱系特异性基因表达的推定驱动因子。最后，免疫致病相关SNP的综合分析表明远端调控元件在疾病病因中的作用。
Naive CD4(+) T cells can differentiate into specific helper and regulatory T cell lineages in order to combat infection and disease. The correct response to cytokines and a controlled balance of these populations is critical for the immune system and the avoidance of autoimmune disorders. To investigate how early cell-fate commitment is regulated, we generated the first human genome-wide maps of histone modifications that reveal enhancer elements after 72 hr of in vitro polarization toward T helper 1 (Th1) and T helper 2 (Th2) cell lineages. Our analysis indicated that even at this very early time point, cell-specific gene regulation and enhancers were at work directing lineage commitment. Further examination of lineage-specific enhancers identified transcription factors (TFs) with known and unknown T cell roles as putative drivers of lineage-specific gene expression. Lastly, an integrative analysis of immunopathogenic-associated SNPs suggests a role for distal regulatory elements in disease etiology.