A cell-specific regulatory region of the human ABO blood group gene regulates the neighborhood gene encoding odorant binding protein 2B.
A cell-specific regulatory region of the human ABO blood group gene regulates the neighborhood gene encoding odorant binding protein 2B.
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DOI：
10.1038/s41598-021-86843-6
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发表时间：
2021-04-01
影响因子：
4.6
通讯作者：
Kominato Y
中科院分区：
文献类型：
--
作者：
Sano R;Takahashi Y;Fukuda H;Harada M;Hayakawa A;Okawa T;Kubo R;Takeshita H;Tsukada J;Kominato Y
人类ABO血型系统在输血和器官移植中具有重要意义。已知 ABO 转录受到 CpG 岛和细胞特异性表达调节区域中的组成型启动子的调节，例如上皮细胞的下游 + 22.6-kb 位点和红系细胞的内含子 1 中的位点。在这里，我们研究了“+”22.6-kb 位点是否可能在编码气味结合蛋白 2B (OBP2B) 的基因的转录调控中发挥作用，该基因位于着丝粒侧，距离“+”22.6-kb 位点 43.4 kb。在胃癌细胞系 KATOIII 中，定量 PCR 分析表明，与野生型细胞相比，使用 CRISPR/Cas9 系统创建的双等位基因删除位点的突变细胞中 OBP2B 和 ABO 转录物的数量显着减少，Western blotting 表明突变细胞中 OBP2B 蛋白的相应减少。此外，单分子荧光原位杂交测定表明，两种转录物的量在单个细胞中是相关的。这些发现表明OBP2B 可能受到ABO 的 + 22.6-kb 位点的共同调节。
The human ABO blood group system is of great importance in blood transfusion and organ transplantation. ABO transcription is known to be regulated by a constitutive promoter in a CpG island and regions for regulation of cell-specific expression such as the downstream + 22.6-kb site for epithelial cells and a site in intron 1 for erythroid cells. Here we investigated whether the + 22.6-kb site might play a role in transcriptional regulation of the gene encoding odorant binding protein 2B (OBP2B), which is located on the centromere side 43.4 kb from the + 22.6-kb site. In the gastric cancer cell line KATOIII, quantitative PCR analysis demonstrated significantly reduced amounts of OBP2B and ABO transcripts in mutant cells with biallelic deletions of the site created using the CRISPR/Cas9 system, relative to those in the wild-type cells, and Western blotting demonstrated a corresponding reduction of OBP2B protein in the mutant cells. Moreover, single-molecule fluorescence in situ hybridization assays indicated that the amounts of both transcripts were correlated in individual cells. These findings suggest that OBP2B could be co-regulated by the + 22.6-kb site of ABO.
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影响因子：
2.9
作者：
Cai, Xiaohong;Jin, Sha;Xiang, Dong
通讯作者：
Xiang, Dong
影响因子：
7
作者：
Battle A;Mostafavi S;Zhu X;Potash JB;Weissman MM;McCormick C;Haudenschild CD;Beckman KB;Shi J;Mei R;Urban AE;Montgomery SB;Levinson DF;Koller D
通讯作者：
Koller D
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
影响因子：
5
作者：
Chihara, Y;Sugano, K;Hirao, Y
通讯作者：
Hirao, Y
影响因子：
4.8
作者：
Kominato, Y;Hata, Y;Yamamoto, F
通讯作者：
Yamamoto, F