Genomewide analysis of Drosophila GAGA factor target genes reveals context-dependent DNA binding.
Genomewide analysis of Drosophila GAGA factor target genes reveals context-dependent DNA binding.
复制标题
果蝇 GAGA 因子靶基因的全基因组分析揭示了背景依赖性 DNA 结合。
DOI：
10.1073/pnas.0438000100
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发表时间：
2003
影响因子：
11.1
通讯作者：
Bussemaker,HarmenJ
中科院分区：
文献类型：
--
作者：
vanSteensel,Bas;Delrow,Jeffrey;Bussemaker,HarmenJ
The association of sequence-specific DNA-binding factors with their cognate target sequencesin vivodepends on the local molecular context, yet this context is poorly understood. To address this issue, we have performed genomewide mapping ofin vivotarget genes ofDrosophilaGAGA factor (GAF). The resulting list of ≈250 target genes indicates that GAF regulates many cellular pathways. We applied unbiased motif-based regression analysis to identify the sequence context that determines GAF binding. Our results confirm that GAF selectively associates with (GA)nrepeat elementsin vivo. GAF binding occurs in upstream regulatory regions, but less in downstream regions. Surprisingly, GAF binds abundantly to introns but is virtually absent from exons, even though the density of (GA)nis roughly the same. Intron binding occurs equally frequently in last introns compared with first introns, suggesting that GAF may not only regulate transcription initiation, but possibly also elongation. We provide evidence for cooperative binding of GAF to closely spaced (GA)nelements and explain the lack of GAF binding to exons by the absence of such closely spaced GA repeats. Our approach for revealing determinants of context-dependent DNA binding will be applicable to many other transcription factors.
