Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells.
Analysis of the FBXO7 promoter reveals overlapping Pax5 and c-Myb binding sites functioning in B cells.
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FBXO 7启动子的分析揭示了重叠的Pax 5和c-MyB结合位点在B细胞中起作用。
DOI：
10.1016/j.bbrc.2021.03.052
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发表时间：
2021-05-21
影响因子：
3.1
通讯作者：
Laman H
中科院分区：
文献类型：
--
作者：
Harris R;Randle S;Laman H
Fbxo7在许多血细胞类型、神经元、少突胶质细胞和精母细胞的分化和功能中起着关键作用。为了深入了解Fbxo7可能发挥关键作用的生理和病理环境，我们试图定义指导Fbxo7表达的转录因子。通过对28个物种的序列比对，我们确定了人类FBXO7启动子，并发现它包含两个富含多个转录因子结合位点的保守区域。其中许多在神经元或造血发育中起作用。利用各种FBXO7启动子报告子，我们发现ELF4、Pax5和c-Myb具有激活转录的功能性结合位点。我们发现内源性Pax5在前b细胞中与FBXO7启动子结合，并且外源性Pax5的表达抑制了早期前b细胞中FBXO7的转录。我们将人类FBXO7启动子定义为从外显子1开始的- 1300到+ 100 bp之间的保守启动子区域。发现了两个保守的转录因子结合位点岛，在24种不同的tf中鉴定出32个推定结合位点（17个在远端区域，15个在近端区域）。ETS因子、ELF4和ELF1、Pax5和c-Myb结合并激活FBXO7荧光素酶报告基因结构。Fbxo7抑制其自身启动子的转录，这是一种不依赖于泛素连接酶的作用。
Fbxo7 is a key player in the differentiation and function of numerous blood cell types, and in neurons, oligodendrocytes and spermatocytes. In an effort to gain insight into the physiological and pathological settings where Fbxo7 is likely to play a key role, we sought to define the transcription factors which direct FBXO7 expression. Using sequence alignments across 28 species, we defined the human FBXO7 promoter and found that it contains two conserved regions enriched for multiple transcription factor binding sites. Many of these have roles in either neuronal or haematopoietic development. Using various FBXO7 promoter reporters, we found ELF4, Pax5 and c-Myb have functional binding sites that activate transcription. We find endogenous Pax5 is bound to the FBXO7 promoter in pre-B cells, and that the exogenous expression of Pax5 represses Fbxo7 transcription in early pro-B cells. We defined the human FBXO7 promoter, as a conserved promoter region between −1300 and + 100 bp from the start of exon 1. Two conserved islands of putative transcription factor binding sites were found with 32 putative binding sites identified for 24 different TFs (17 in the distal region; 15 in the proximal region). ETS factors, ELF4 and ELF1, and Pax5 and c-Myb bind and activate FBXO7 luciferase reporter constructs. Fbxo7 represses transcription from its own promoter, and this is a ubiquitin ligase-independent effect.
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影响因子：
64.8
作者：
Mullighan, Charles G.;Goorha, Salil;Downing, James R.
通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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