Temporal and spatial control of murine GATA-3 transcription by promoter-proximal regulatory elements
Temporal and spatial control of murine GATA-3 transcription by promoter-proximal regulatory elements
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DOI：
10.1006/dbio.1997.8575
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发表时间：
1997-08-01
影响因子：
2.7
通讯作者：
Engel, JD
中科院分区：
文献类型：
--
作者：
Lieuw, KH;Li, GL;Engel, JD
GATA-3以时间动态的方式表达，并在脊椎动物胎儿发育过程中发挥重要作用。纯合子mGATA-3突变胚胎在妊娠中期死亡，从而使其在胚胎发生期间表达的许多组织中对特定细胞命运发展的贡献的分析复杂化。我们在这里表明，控制GATA-3调控的元件可以通过转基因小鼠精确地细化到离散的顺式作用域：在转录起始位点周围6 kb内，发现了控制早期肌肉块、PNS神经元子集、生殖器结节和鳃裂拱中mGATA-3表达的单独序列。鳃弓调控元件特别强大，并被细化为位于转录起始位点nt -2832和-2462之间的离散增强子序列。增强子含有许多已被充分表征的转录因子的潜在结合位点，这表明mGATA-3的转录活性可能受到这些蛋白（或相关家族成员）在促进颌骨形成的弓间质中的调节。这些研究表明，复杂发育过程所需的离散调控元件可以单独定位，这表明个体转录因子的发育瞬态表达协同促进了细胞分化的时间和空间模式，从而导致成人解剖结构的形成。(C) 1997学术出版社。
GATA-3 is expressed in a temporally dynamic manner and fulfills vital functions during vertebrate fetal development. Homozygous mGATA-3 mutant embryos die at midgestation, thus complicating the analysis of its contribution to the development of specific cell fates in the many tissues where it is expressed during embryogenesis. We show here that the elements controlling GATA-3 regulation can be precisely refined, using transgenic mice, to discrete cis-acting domains: within 6 kb surrounding the transcriptional initiation site, separate sequences were found to control the expression of mGATA-3 in early muscle masses, in a subset of PNS neurons, in the genital tubercle, and in the branchial arches. The branchial arch regulatory element is particularly robust and was refined to a discrete enhancer sequence lying between nt -2832 and -2462 from the transcription initiation site. The enhancer contains potential binding sites for many well-characterized transcription factors, suggesting that mGATA-3 transcriptional activity may be regulated by these proteins (or related family members) in the mesenchyme of the arches that contribute to formation of the jaw. These studies show that discrete regulatory elements required for the elaboration of complex developmental programs can be individually localized, suggesting that the developmentally transient expression of individual transcription factors collaboratively contributes to the temporal and spatial pattern of cellular differentiation leading to the formation of adult anatomy. (C) 1997 Academic Press.