Department of Cell Biology, Erasmus Medical Center, 3015GE Rotterdam, The Netherlands.
Genes Dev. 2010 Feb 1;24(3):277-89. doi: 10.1101/gad.551810.
One of the complexes formed by the hematopoietic transcription factor Gata1 is a complex with the Ldb1 (LIM domain-binding protein 1) and Tal1 proteins. It is known to be important for the development and differentiation of the erythroid cell lineage and is thought to be implicated in long-range interactions. Here, the dynamics of the composition of the complex-in particular, the binding of the negative regulators Eto2 and Mtgr1-are studied, in the context of their genome-wide targets. This shows that the complex acts almost exclusively as an activator, binding a very specific combination of sequences, with a positioning relative to transcription start site, depending on the type of the core promoter. The activation is accompanied by a net decrease in the relative binding of Eto2 and Mtgr1. A Chromosome Conformation Capture sequencing (3C-seq) assay also shows that the binding of the Ldb1 complex marks genomic interaction sites in vivo. This establishes the Ldb1 complex as a positive regulator of the final steps of erythroid differentiation that acts through the shedding of negative regulators and the active interaction between regulatory sequences.
造血转录因子 Gata1 形成的复合物之一是与 Ldb1（LIM 结构域结合蛋白 1）和 Tal1 蛋白形成的复合物。该复合物对于红细胞谱系的发育和分化非常重要，并且被认为与长距离相互作用有关。在这里，研究了该复合物组成的动态变化——特别是负调控因子 Eto2 和 Mtgr1 的结合——在其全基因组靶标的背景下进行。这表明该复合物几乎完全作为一种激活剂起作用，结合了非常特定的序列组合，其相对于转录起始位点的位置取决于核心启动子的类型。激活伴随着 Eto2 和 Mtgr1 的相对结合的净减少。染色体构象捕获测序（3C-seq）试验还表明，Ldb1 复合物的结合标志着体内基因组相互作用位点。这确立了 Ldb1 复合物作为红细胞分化最后阶段的正调控因子，通过负调控因子的脱落和调控序列之间的主动相互作用发挥作用。
