Defining the CREB regulon: A genome-wide analysis of transcription factor regulatory regions
Defining the CREB regulon: A genome-wide analysis of transcription factor regulatory regions
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DOI：
10.1016/j.cell.2004.10.032
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发表时间：
2004-12-29
期刊：
影响因子：
64.5
通讯作者：
Goodman, RH
中科院分区：
文献类型：
--
作者：
Impey, S;McCorkle, SR;Goodman, RH
CREB 转录因子调节分化、存活和突触可塑性。然而，负责这些应对措施的 CREB 目标的补充尚未确定。我们通过将染色质免疫沉淀 (ChIP) 与 SAGE 修饰相结合，开发了一种识别 CREB 靶标的新方法，称为染色质占用序列分析 (SACO)。使用源自大鼠 PC12 细胞的 SACO 文库，我们鉴定了类似于 41,000 个映射到独特基因组位点的基因组特征标签 (GST)。 CREB 结合已在多个 GST 支持的所有位点上得到证实。在通过多个 GST 鉴定的 6302 个位点中，40% 位于注释基因转录起始点的 2 kb 范围内，49% 位于 CpG 岛的 1 kb 范围内，72% 位于推定的 cAMP 响应元件 (CRE) 的 1 kb 范围内。 SACO 基因座的很大一部分描绘了双向启动子和新的反义转录本。这项研究代表了后生动物物种中转录因子结合位点的最全面的定义。
The CREB transcription factor regulates differentiation, survival, and synaptic plasticity. The complement of CREB targets responsible for these responses has not been identified, however. We developed a novel approach to identify CREB targets, termed serial analysis of chromatin occupancy (SACO), by combining chromatin immunoprecipitation (ChIP) with a modification of SAGE. Using a SACO library derived from rat PC12 cells, we identified similar to41,000 genomic signature tags (GSTs) that mapped to unique genomic loci. CREB binding was confirmed for all loci supported by multiple GSTs. Of the 6302 loci identified by multiple GSTs, 40% were within 2 kb of the transcriptional start of an annotated gene, 49% were within 1 kb of a CpG island, and 72% were within 1 kb of a putative cAMP-response element (CRE). A large fraction of the SACO loci delineated bidirectional promoters and novel antisense transcripts. This study represents the most comprehensive definition of transcription factor binding sites in a metazoan species.