Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors.
Comprehensive characterization of erythroid-specific enhancers in the genomic regions of human Krüppel-like factors.
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人类 Krüppel 样因子基因组区域中红细胞特异性增强子的综合表征
DOI：
10.1186/1471-2164-14-587
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发表时间：
2013-08-28
期刊：
影响因子：
4.4
通讯作者：
Fang X
中科院分区：
文献类型：
--
作者：
Xiong Q;Zhang Z;Chang KH;Qu H;Wang H;Qi H;Li Y;Ruan X;Yang Y;Yang Y;Li Y;Sandstrom R;Sabo PJ;Li Q;Stamatoyannopoulos G;Stamatoyannopoulos JA;Fang X
dna酶I超敏感位点（DHSs）的定位是实验鉴定基因调控元件（CREs）的有力工具。在cre中，增强子数量丰富，主要作用于驱动细胞特异性基因表达。kr<s:1> ppel样因子（KLFs）是一类真核生物转录因子。一些klf已被证明在造血中发挥重要作用。然而，通过CREs，特别是增强子，在红系细胞中对KLFs的转录调控知之甚少。结果在17个人KLFs的基因组区域，通过dna -seq鉴定出23个红系特异性或推测红系特异性dhs，并利用双荧光素酶报告基因（DLR）测定了它们的增强子活性。在23个红细胞特异性DHSs中，有15个DHSs在驱动最小启动子（minP）方面的活性与经典增强子HS2相当。在红细胞中，15个dhs在驱动相应的KLF启动子（KLF- ps）时发挥增强子的作用，其中一些与增加minP活性的dhs重叠；其中，10个dhs最终被鉴定为红细胞特异性KLF增强子。利用染色质免疫沉淀结合测序（ChIP-seq）数据进行生物信息学和生化分析，进一步证实了这10个红细胞特异性KLF增强子。结论本研究为从高通量测序获得的dhs中广泛鉴定基因和细胞特异性增强子提供了一种可行的策略，有助于揭示基因在某些特定细胞中的转录调控和生物学功能。
BackgroundMapping of DNase I hypersensitive sites (DHSs) is a powerful tool to experimentally identifycis-regulatory elements (CREs). Among CREs, enhancers are abundant and predominantly act in driving cell-specific gene expression. Krüppel-like factors (KLFs) are a family of eukaryotic transcription factors. Several KLFs have been demonstrated to play important roles in hematopoiesis. However, transcriptional regulation of KLFs via CREs, particularly enhancers, in erythroid cells has been poorly understood.ResultsIn this study, 23 erythroid-specific or putative erythroid-specific DHSs were identified by DNase-seq in the genomic regions of 17 human KLFs, and their enhancer activities were evaluated using dual-luciferase reporter (DLR) assay. Of the 23 erythroid-specific DHSs, the enhancer activities of 15 DHSs were comparable to that of the classical enhancer HS2 in driving minimal promoter (minP). Fifteen DHSs, some overlapping those that increased minP activities, acted as enhancers when driving the corresponding KLF promoters (KLF-Ps) in erythroid cells; of these, 10 DHSs were finally characterized as erythroid-specific KLF enhancers. These 10 erythroid-specific KLF enhancers were further confirmed using chromatin immunoprecipitation coupled to sequencing (ChIP-seq) data-based bioinformatic and biochemical analyses.ConclusionOur present findings provide a feasible strategy to extensively identify gene- and cell-specific enhancers from DHSs obtained by high-throughput sequencing, which will help reveal the transcriptional regulation and biological functions of genes in some specific cells.
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影响因子：
64.8
作者：
Heintzman, Nathaniel D.;Hon, Gary C.;Hawkins, R. David;Kheradpour, Pouya;Stark, Alexander;Harp, Lindsey F.;Ye, Zhen;Lee, Leonard K.;Stuart, Rhona K.;Ching, Christina W.;Ching, Keith A.;Antosiewicz-Bourget, Jessica E.;Liu, Hui;Zhang, Xinmin;Green, Roland D.;Lobanenkov, Victor V.;Stewart, Ron;Thomson, James A.;Crawford, Gregory E.;Kellis, Manolis;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
20.3
作者：
Basu, Priyadarshi;Lung, Tina K.;Lloyd, Joyce A.
通讯作者：
Lloyd, Joyce A.
影响因子：
64.5
作者：
Hallikas, O;Palin, K;Taipale, J
通讯作者：
Taipale, J
影响因子：
30.8
作者：
John S;Sabo PJ;Thurman RE;Sung MH;Biddie SC;Johnson TA;Hager GL;Stamatoyannopoulos JA
通讯作者：
Stamatoyannopoulos JA
影响因子：
21.3
作者：
Jiang, Jianming;Chan, Yun-Shen;Ng, Huck-Hui
通讯作者：
Ng, Huck-Hui