Comprehensively Profiling the Chromatin Architecture of Tissue Restricted Antigen Expression in Thymic Epithelial Cells Over Development.
Comprehensively Profiling the Chromatin Architecture of Tissue Restricted Antigen Expression in Thymic Epithelial Cells Over Development.
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DOI：
10.3389/fimmu.2018.02120
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发表时间：
2018
影响因子：
7.3
通讯作者：
Holländer GA
中科院分区：
文献类型：
--
作者：
Handel AE;Shikama-Dorn N;Zhanybekova S;Maio S;Graedel AN;Zuklys S;Ponting CP;Holländer GA
胸腺上皮细胞（TEC）在胸腺生成中起着重要作用，包括控制胸腺细胞的负选择。这个过程依赖于它们混杂表达编码组织限制性抗原的基因的能力。这种能力在髓质TEC（mTEC）中部分地通过转录促进剂自身免疫调节剂AIRE的存在来实现。AIRE调控的基因转录以抑制性染色质修饰为标志，包括H3 K27 me 3。然而，在TEC发育期间，这些染色质标记何时建立仍不清楚。在这里，我们使用不同TEC亚型中多种染色质修饰的综合ChIP-seq数据集来证明染色质景观在TEC分化早期建立。发现在成熟mTEC中发现的许多染色质结构已经存在于mTEC谱系分化的早期阶段以及非TEC组织中。这反映在以下事实中：机器学习方法准确地将基因分类为未成熟和成熟mTEC中的AIRE诱导的或AIRE独立的。此外，TEC特异性增强子元件的分析确定候选转录因子可能是重要的mTEC的发展和功能。我们的研究结果表明，成熟的mTEC染色质景观奠定了mTEC分化的早期，和AIRE是不需要的大规模重新图案化的染色质在mTEC。
Thymic epithelial cells (TEC) effect crucial roles in thymopoiesis including the control of negative thymocyte selection. This process depends on their capacity to express promiscuously genes encoding tissue-restricted antigens. This competence is accomplished in medullary TEC (mTEC) in part by the presence of the transcriptional facilitator AutoImmune REgulator, AIRE. AIRE-regulated gene transcription is marked by repressive chromatin modifications, including H3K27me3. When during TEC development these chromatin marks are established, however, remains unclear. Here we use a comprehensive ChIP-seq dataset of multiple chromatin modifications in different TEC subtypes to demonstrate that the chromatin landscape is established early in TEC differentiation. Much of the chromatin architecture found in mature mTEC was found to be present already over earlier stages of mTEC lineage differentiation as well as in non-TEC tissues. This was reflected by the fact that a machine learning approach accurately classified genes as AIRE-induced or AIRE-independent both in immature and mature mTEC. Moreover, analysis of TEC specific enhancer elements identified candidate transcription factors likely to be important in mTEC development and function. Our findings indicate that the mature mTEC chromatin landscape is laid down early in mTEC differentiation, and that AIRE is not required for large-scale re-patterning of chromatin in mTEC.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
30.5
作者：
Brennecke P;Reyes A;Pinto S;Rattay K;Nguyen M;Küchler R;Huber W;Kyewski B;Steinmetz LM
通讯作者：
Steinmetz LM
影响因子：
30.5
作者：
Bansal K;Yoshida H;Benoist C;Mathis D
通讯作者：
Mathis D
影响因子：
3.1
作者：
Olden, JD;Joy, MK;Death, RG
通讯作者：
Death, RG
影响因子：
30.5
作者：
Herzig, Yonatan;Nevo, Shir;Abramson, Jakub
通讯作者：
Abramson, Jakub