Transcription start sites and usage of the first exon of mouse Foxp3 gene

Transcription start sites and usage of the first exon of mouse Foxp3 gene
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DOI:
10.1007/s11033-012-1825-3
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发表时间:
2012-10-01
影响因子:
2.8
通讯作者:
Fujii, Hodaka
Fujii, Hodaka
中科院分区:
生物学4区
文献类型:
--
作者:
Fujita, Toshitsugu;Fujii, Hodaka

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主分化转录因子(MDFs)在细胞谱系定型和细胞功能中起决定性作用。叉头盒P3(Forkhead box P3,Foxp 3)是调节性T细胞(Regulatory T cells,Tcells)的谱系定型和抑制功能所必需的转录因子,在自身免疫抑制中起重要作用。在这里,我们分析了转录起始位点(TSS)和使用的第一个外显子的小鼠Foxp 3(mFoxp 3)基因。除了已知的第一外显子-2a和-2b外,我们还发现了一个新的第一外显子,-2b Delta,它是外显子-2b的3 '截短形式。外显子-2b Delta的主要TSS与外显子-2b相同。与具有主要TSS的外显子-2b和-2b Delta相反,外显子-2a具有多个TSS。实时荧光定量RT-PCR结果表明,mFoxp 3基因的第一外显子是外显子-2b。mFoxp 3的第一个外显子的使用在女性和男性中是相当的。具有不同第一外显子的mFoxp 3转录物使用相同的下游外显子。因此,第一外显子的选择有助于在小鼠胸腺中产生mFoxp 3转录物的多样性。
Master differentiation transcription factors (MDFs) play decisive roles in cell lineage commitment and cellular functions. Forkhead box P3 (Foxp3) is the MDF essential for the lineage commitment and the suppression function of regulatory T cells (Tregs), which play critical roles in suppression of autoimmunity. Here, we analyzed transcription start sites (TSSs) and usage of the first exon of the mouse Foxp3 (mFoxp3) gene. In addition to known first exons -2a and -2b, we found a novel first exon, -2b Delta, which was the 3'-truncated form of the exon -2b. The major TSS of the exon -2b Delta was identical with that of the exon -2b. In contrast to the exon -2b and -2b Delta that have a major TSS, the exon -2a had multiple TSSs. Quantitative real-time RT-PCR revealed that the majority of mFoxp3 transcripts utilize the exon -2b as the first exon. Usage of the first exon of mFoxp3 was comparable in female and male Tregs. mFoxp3 transcripts with different first exons used the same downstream exons. Thus, selection of the first exons contributes to generation of diversity of mFoxp3 transcripts in mouse Tregs.