SET-NUP214 and MLL cooperatively regulate the promoter activity of the HoxA10 gene,Genes to Cells

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SET-NUP214 and MLL cooperatively regulate the promoter activity of the HoxA10 gene
Genes to Cells ( IF 1.3 ) Pub Date : 2021-07-28 , DOI: 10.1111/gtc.12886
Sadik Cigdem _{1,

2} , Shoko Saito ₁ , Daiki Nishikata ₁ , Kyosuke Nagata ₃ , Mitsuru Okuwaki ₁

Affiliation

SET-Nup214 is a recurrent fusion gene that is mainly observed in T-cell acute lymphoblastic leukemia (T-ALL). Dysregulation of homeobox (Hox) genes is frequently observed in patients with leukemia. Consistent with this, HoxA genes are upregulated in the SET-Nup214 ⁺ T-ALL cell line and patients. Although SET-Nup214 has been reported to be recruited to the promoter regions of HoxA genes, the detailed mechanisms of how SET-Nup214 specifically binds to HoxA gene promoters and regulates HoxA gene expression are not known. In this study, we demonstrated that SET-Nup214 interacts with MLL via the SET acidic region of SET-Nup214. SET-Nup214 and MLL cooperatively enhance the promoter activity of the HoxA10 gene. Neither the SET region alone nor the Nup214 region alone sufficiently enhanced the HoxA10 gene promoter. Our results indicated that the SET portion of the SET-Nup214-fusion protein is important for interactions with MLL and transcription enhancement of the HoxA10 gene. Thus, our study will contribute to the understanding of how SET-Nup214 and MLL disturb the expression of HoxA10 gene in leukemia.

中文翻译：

SET-NUP214 和 MLL 协同调控 HoxA10 基因的启动子活性

SET-Nup214是一种复发性融合基因，主要在 T 细胞急性淋巴细胞白血病 (T-ALL) 中观察到。在白血病患者中经常观察到同源框( Hox ) 基因的失调。与此一致，HoxA基因在SET-Nup214 ⁺ T-ALL 细胞系和患者中上调。尽管据报道 SET-Nup214 被招募到 HoxA 基因的启动子区域，但SET-Nup214 如何特异性结合HoxA基因启动子并调节HoxA的详细机制基因表达未知。在这项研究中，我们证明了 SET-Nup214 通过 SET-Nup214 的 SET 酸性区域与 MLL 相互作用。SET-Nup214 和 MLL 协同增强HoxA10基因的启动子活性。单独的 SET 区域和单独的 Nup214 区域都不能充分增强HoxA10基因启动子。我们的结果表明，SET-Nup214 融合蛋白的 SET 部分对于与 MLL 的相互作用和HoxA10基因的转录增强很重要。因此，我们的研究将有助于理解 SET-Nup214 和 MLL 如何干扰HoxA10基因在白血病中的表达。

更新日期：2021-07-28

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