Department of Cell and Developmental Biology, 3071 BSRB, 109 Zina Pitcher Place, University of Michigan Medical School, Ann Arbor, MI 48103, USA.
Mol Cell Biol. 2011 May;31(9):1894-904. doi: 10.1128/MCB.05065-11. Epub 2011 Mar 7.
Transcription factor GATA-3 is vital for multiple stages of T cell and natural killer (NK) cell development, and yet the factors that directly regulate Gata3 transcription during hematopoiesis are only marginally defined. Here, we show that neither of the Gata3 promoters, previously implicated in its tissue-specific regulation, is alone capable of directing Gata3 transcription in T lymphocytes. In contrast, by surveying large swaths of DNA surrounding the Gata3 locus, we located a cis element that can recapitulate aspects of the Gata3-dependent T cell regulatory program in vivo. This element, located 280 kbp 3' to the structural gene, directs both T cell- and NK cell-specific transcription in vivo but harbors no other tissue activity. This novel, distant element regulates multiple major developmental stages that require GATA-3 activity.
转录因子 GATA-3 对于 T 细胞和自然杀伤 (NK) 细胞的多个发育阶段至关重要，但在造血过程中直接调节 Gata3 转录的因素仅略有定义。在这里，我们表明，以前涉及组织特异性调节的 Gata3 启动子都不能单独在 T 淋巴细胞中指导 Gata3 转录。相比之下，通过对 Gata3 基因座周围的大片 DNA 进行调查，我们找到了一个顺式元件，该元件可以在体内重现 Gata3 依赖的 T 细胞调控程序的某些方面。该元件位于结构基因的 3'侧 280 kbp 处，可在体内指导 T 细胞和 NK 细胞特异性转录，但不具有其他组织活性。这个新的、遥远的元件调节需要 GATA-3 活性的多个主要发育阶段。
