TFII-I/Gtf2i and Erythro-Megakaryopoiesis.

TFII-I/Gtf2i and Erythro-Megakaryopoiesis.
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DOI:
10.3389/fphys.2020.590180
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发表时间:
2020
影响因子:
4
通讯作者:
Bungert J
Bungert J
中科院分区:
医学2区
文献类型:
--
作者:
Gurumurthy A;Wu Q;Nar R;Paulsen K;Trumbull A;Fishman RC;Brand M;Strouboulis J;Qian Z;Bungert J

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TFII-I是一种广泛表达的转录因子,可正向或负向调节基因表达。TFII-I与神经和免疫疾病以及胸腺上皮癌有关。Williams-Beuren综合征(WBS)是由染色体7q11.23上的一个大的半合子缺失引起的,该缺失包括26-28个基因,包括编码TFII-I的人类基因GTF 2 I。最近,一部分WBS患者表现为红细胞增多症,这是一种以红细胞增大为特征的轻度贫血。我们通过三苯氧胺诱导的Cre重组,在成年小鼠中有条件地缺失TFII-I/Gtf 2 i基因。骨髓细胞显示红-巨核细胞生成缺陷和成人β-珠蛋白基因表达增加。数据显示TFII-I充当β-珠蛋白基因转录的阻遏物,并且其涉及红-巨核细胞的分化。
TFII-I is a ubiquitously expressed transcription factor that positively or negatively regulates gene expression. TFII-I has been implicated in neuronal and immunologic diseases as well as in thymic epithelial cancer. Williams–Beuren Syndrome (WBS) is caused by a large hemizygous deletion on chromosome 7q11.23 which encompasses 26–28 genes, including GTF2I, the human gene encoding TFII-I. A subset of WBS patients has recently been shown to present with macrocytosis, a mild anemia characterized by enlarged erythrocytes. We conditionally deleted the TFII-I/Gtf2i gene in adult mice by tamoxifen induced Cre-recombination. Bone marrow cells revealed defects in erythro-megakaryopoiesis and an increase in expression of the adult β-globin gene. The data show that TFII-I acts as a repressor of β–globin gene transcription and that it is implicated in the differentiation of erythro-megakaryocytic cells.
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