Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation.
Genome-wide investigation of in vivo EGR-1 binding sites in monocytic differentiation.
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DOI：
10.1186/gb-2009-10-4-r41
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发表时间：
2009
期刊：
影响因子：
12.3
通讯作者：
Hayashizaki Y
中科院分区：
文献类型：
--
作者：
Kubosaki A;Tomaru Y;Tagami M;Arner E;Miura H;Suzuki T;Suzuki M;Suzuki H;Hayashizaki Y
EGR-1结合位点的全基因组分析揭示了与CpG岛和组蛋白H3赖氨酸9结合的共定位。EGR-1结合位点附近的SP-1结合位置显著改变。即刻早期基因被认为在暴露于适当刺激后的动态基因调控网络中起重要作用。早期生长反应基因1（EGR-1）是一种立即早期基因，它与人单核母细胞瘤细胞沿着用佛波醇酯处理后的单核细胞定型的分化有关。EGR-1被认为是单细胞生成的调节剂，但EGR-1在单核细胞分化中的确切功能尚未完全阐明。我们通过染色质免疫沉淀与启动子阵列（ChIP芯片）进行了第一次全基因组EGR-1结合位点分析，并确定了分化THP-1细胞中的EGR-1靶位点。通过将结果与先前报道的FANTOM 4数据相结合，我们发现EGR-1结合位点与CpG岛、乙酰化组蛋白H3赖氨酸9结合位点和CAGE标签簇高度共定位。基因本体（GO）分析揭示了EGR-1靶基因中丰富的术语，包括分子的结合。此外，与基因表达谱数据的比较表明，EGR-1结合影响基因表达。此外，PMA刺激后DNA结合蛋白的体内占位变化的观察表明，EGR-1结合位点附近的SP1结合占位发生了显着变化。我们得出结论，EGR-1主要识别活性基因启动子中富含GC的共有序列。GO分析和基因表达谱数据证实，EGR-1参与细胞事件中信息传递的启动。对EGR-1和SP1在体内占有率变化的观察表明，EGR-1和其他蛋白质之间的几种类型的相互作用导致对EGR-1下游基因的多种反应。
A Genome-wide analysis of EGR-1 binding sites reveals co-localization with CpG islands and histone H3 lysine 9 binding. SP-1 binding occupancies near EGR-1 binding sites are dramatically altered. Immediate early genes are considered to play important roles in dynamic gene regulatory networks following exposure to appropriate stimuli. One of the immediate early genes, early growth response gene 1 (EGR-1), has been implicated in differentiation of human monoblastoma cells along the monocytic commitment following treatment with phorbol ester. EGR-1 has been thought to work as a modifier of monopoiesis, but the precise function of EGR-1 in monocytic differentiation has not been fully elucidated. We performed the first genome-wide analysis of EGR-1 binding sites by chromatin immunoprecipitation with promoter array (ChIP-chip) and identified EGR-1 target sites in differentiating THP-1 cells. By combining the results with previously reported FANTOM4 data, we found that EGR-1 binding sites highly co-localized with CpG islands, acetylated histone H3 lysine 9 binding sites, and CAGE tag clusters. Gene Ontology (GO) analysis revealed enriched terms, including binding of molecules, in EGR-1 target genes. In addition, comparison with gene expression profiling data showed that EGR-1 binding influenced gene expression. Moreover, observation of in vivo occupancy changes of DNA binding proteins following PMA stimulation indicated that SP1 binding occupancies were dramatically changed near EGR-1 binding sites. We conclude that EGR-1 mainly recognizes GC-rich consensus sequences in promoters of active genes. GO analysis and gene expression profiling data confirm that EGR-1 is involved in initiation of information transmission in cell events. The observations of in vivo occupancy changes of EGR-1 and SP1 suggest that several types of interplay between EGR-1 and other proteins result in multiple responses to EGR-1 downstream genes.
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影响因子：
64.5
作者：
NGUYEN, HQ;HOFFMANLIEBERMANN, B;LIEBERMANN, DA
通讯作者：
LIEBERMANN, DA
影响因子：
20.3
作者：
Guha, M;O'Connell, MA;Mackman, N
通讯作者：
Mackman, N
影响因子：
11.4
作者：
Rossi, D;Cozzio, A;Weissmann, C
通讯作者：
Weissmann, C
影响因子：
64.5
作者：
Laslo, Peter;Spooner, Chauncey J.;Singh, Harinder
通讯作者：
Singh, Harinder
影响因子：
82.9
作者：
Fahmy, RG;Dass, CR;Khachigian, LM
通讯作者：
Khachigian, LM