期刊
DEVELOPMENT
卷 136, 期 5, 页码 749-760出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.024703
关键词
Enhancer prediction; Gene regulation; No tail/brachyury; Spadetail/tbx16
资金
- March of Dimes Birth Defects Foundation [1-FY05-118]
- Wellcome Trust Program Grant
- MRC Career Development Award
- Lister Institute Research Prize
- U.C. Berkeley Center for Integrative Genomics
- MRC [G0700213] Funding Source: UKRI
- Medical Research Council [G0700213, G0300723B] Funding Source: researchfish
The zebrafish genes spadetail (spt) and no tail (ntl) encode T-box transcription factors that are important for early mesoderm development. Although much has been done to characterize these genes, the identity and location of target regulatory elements remain largely unknown. Here, we survey the genome for downstream target genes of the Spt and Ntl T-box transcription factors. We find evidence for extensive additive interactions towards gene activation and limited evidence for combinatorial and antagonistic interactions between the two factors. Using in vitro binding selection assays to define Spt- and Ntl-binding motifs, we searched for target regulatory sequence via a combination of binding motif searches and comparative genomics. We identified regulatory elements for tbx6 and deltaD, and, using chromatin immunoprecipitation, in vitro DNA binding assays and transgenic methods, we provide evidence that both are directly regulated by T-box transcription factors. We also find that deltaD is directly activated by T-box factors in the tail bud, where it has been implicated in starting the segmentation clock, suggesting that spt and ntl act upstream of this process.
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