Hwang Eun Sook, Szabo Susanne J, Schwartzberg Pamela L, Glimcher Laurie H
Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA.
Science. 2005 Jan 21;307(5708):430-3. doi: 10.1126/science.1103336.
Cell lineage specification depends on both gene activation and gene silencing, and in the differentiation of T helper progenitors to Th1 or Th2 effector cells, this requires the action of two opposing transcription factors, T-bet and GATA-3. T-bet is essential for the development of Th1 cells, and GATA-3 performs an equivalent role in Th2 development. We report that T-bet represses Th2 lineage commitment through tyrosine kinase-mediated interaction between the two transcription factors that interferes with the binding of GATA-3 to its target DNA. These results provide a novel function for tyrosine phosphorylation of a transcription factor in specifying alternate fates of a common progenitor cell.
细胞谱系特化依赖于基因激活和基因沉默，在T辅助祖细胞分化为Th1或Th2效应细胞的过程中，这需要两种相互拮抗的转录因子T-bet和GATA-3发挥作用。T-bet对Th1细胞的发育至关重要，而GATA-3在Th2细胞发育中发挥同等作用。我们报告称，T-bet通过酪氨酸激酶介导的两种转录因子之间的相互作用抑制Th2谱系定向分化，这种相互作用会干扰GATA-3与其靶DNA的结合。这些结果为转录因子的酪氨酸磷酸化在确定共同祖细胞的不同命运方面提供了一种新功能。
