Transcriptional regulation of vav, a gene expressed throughout the hematopoietic compartment
Transcriptional regulation of vav, a gene expressed throughout the hematopoietic compartment
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DOI：
10.1182/blood.v91.2.419.419_419_430
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发表时间：
1998-01-15
期刊：
影响因子：
20.3
通讯作者：
Adams, JM
中科院分区：
文献类型：
--
作者：
Ogilvy, S;Elefanty, AG;Adams, JM
vav基因在所有造血细胞中表达，但很少在其他细胞类型中表达。为了探索其不寻常的全隔室调控，我们克隆了小鼠基因，对其启动子区进行测序，鉴定了染色质中的DNase I超敏感（HS）位点，并在细胞系和转基因小鼠中用β-半乳糖苷酶（β-gal）报告基因测试了其启动子活性。而成纤维细胞没有HS位点，髓系和红系细胞系含有5个，位于转录起始点上游0.2 kb（HS 1）、1.9 kb（HS 2）和3.6 kb（HS 3），下游0.6 kb（HS 4）和10 kb（HS 5）。一个vav的DNA片段，包括HS 1促进β-半乳糖在骨髓中的表达，但不是成纤维细胞系。在转基因小鼠的白细胞中的表达也需要HS 2和HS 5。只有造血器官含有β-gal，但几乎所有β-gal（+）细胞都是B或T淋巴细胞。表达总是多样化的（马赛克），β-gal（+）细胞的比例随着淋巴成熟和动物年龄的增加而下降。因此，这些vav调控元件促进了体内造血特异性表达，至少在淋巴细胞中，但转基因偶尔沉默。维持泛造血表达可能需要额外的vav元件或替代报告基因。(C)1998年，美国血液学会。
The vav gene is expressed in all hematopoietic but few other cell types. To explore its unusual compartment-wide regulation, We cloned the murine gene, sequenced its promoter region, identified DNase I hypersensitive (HS) sites in the chromatin, and tested their promoter activity with a beta-galactosidase (beta-gal) reporter gene in cell lines and transgenic mice. Whereas fibroblasts had no HS sites, a myeloid and an erythroid cell line contained five, located 0.2 kb (HS1), 1.9 kb (HS2), and 3.6 kb (HS3) upstream from the transcription start and 0.6 kb (HS4) and 10 kb (HS5) downstream. A vav DNA fragment including HS1 promoted beta-gal expression in a myeloid but not a fibroblast line. Expression in leukocytes of transgenic mice also required HS2 and HS5. Only hematopoietic organs contained beta-gal, but virtually all beta-gal(+) cells were B or T lymphocytes. Expression was always variegated (mosaic), and the proportion of beta-gal(+) cells declined with lymphoid maturation and animal age. Thus, these vav regulatory elements promoted hematopoietic-specific expression in vivo, at least in lymphocytes, but the transgene was sporadically silenced. Maintaining pan-hematopoietic expression may require additional vav elements or an alternative reporter. (C) 1998 by The American Society of Hematology.