Department of Cell Biology and Center for Biomedical Genetics, Erasmus Medical Center, Rotterdam, Netherlands.
Mol Cell Biol. 2012 Oct;32(19):3814-22. doi: 10.1128/MCB.05938-11. Epub 2012 Jul 16.
RUNX1 is known to be an essential transcription factor for generating hematopoietic stem cells (HSC), but much less is known about its role in the downstream process of hematopoietic differentiation. RUNX1 has been shown to be part of a large transcription factor complex, together with LDB1, GATA1, TAL1, and ETO2 (N. Meier et al., Development 133:4913-4923, 2006) in erythroid cells. We used a tagging strategy to show that RUNX1 interacts with two novel protein partners, LSD1 and MYEF2, in erythroid cells. MYEF2 is bound in undifferentiated cells and is lost upon differentiation, whereas LSD1 is bound in differentiated cells. Chromatin immunoprecipitation followed by sequencing (ChIP-seq) and microarray expression analysis were used to show that RUNX1 binds approximately 9,000 target sites in erythroid cells and is primarily active in the undifferentiated state. Functional analysis shows that a subset of the target genes is suppressed by RUNX1 via the newly identified partner MYEF2. Knockdown of Myef2 expression in developing zebrafish results in a reduced number of HSC.
RUNX1 是生成造血干细胞 (HSC) 的必需转录因子，但对其在造血分化下游过程中的作用知之甚少。RUNX1 已被证明是一个大型转录因子复合物的一部分，与 LDB1、GATA1、TAL1 和 ETO2（N. Meier 等人，Development 133:4913-4923, 2006）一起存在于红细胞中。我们使用标记策略表明，RUNX1 在红细胞中与两个新的蛋白伴侣 LSD1 和 MYEF2 相互作用。MYEF2 在未分化细胞中结合，并在分化时丢失，而 LSD1 在分化细胞中结合。染色质免疫沉淀测序 (ChIP-seq) 和微阵列表达分析表明，RUNX1 在红细胞中结合了大约 9000 个靶位点，主要在未分化状态下具有活性。功能分析表明，靶基因的一个亚组通过新鉴定的伙伴 MYEF2 被 RUNX1 抑制。在发育中的斑马鱼中敲低 Myef2 表达会导致 HSC 数量减少。
