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TAF10 Interacts with the GATA1 Transcription Factor and Controls Mouse Erythropoiesis

机译：TAF10与GATA1转录因子相互作用并控制小鼠促红细胞生成。

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The ordered assembly of a functional preinitiation complex (PIC), composed of general transcription factors (GTFs), is a prerequisite for the transcription of protein-coding genes by RNA polymerase II. TFIID, comprised of the TATA binding protein (TBP) and 13 TBP-associated factors (TAFs), is the GTF that is thought to recognize the promoter sequences allowing site-specific PIC assembly. Transcriptional cofactors, such as SAGA, are also necessary for tightly regulated transcription initiation. The contribution of the two TAF10-containing complexes (TFIID, SAGA) to erythropoiesis remains elusive. By ablating TAF10 specifically in erythroid cells in vivo, we observed a differentiation block accompanied by deregulated GATA1 target genes, including Gata1 itself, suggesting functional cross talk between GATA1 and TAF10. Additionally, we analyzed by mass spectrometry the composition of TFIID and SAGA complexes in mouse and human cells and found that their global integrity is maintained, with minor changes, during erythroid cell differentiation and development. In agreement with our functional data, we show that TAF10 interacts directly with GATA1 and that TAF10 is enriched on the GATA1 locus in human fetal erythroid cells. Thus, our findings demonstrate a cross talk between canonical TFIID and SAGA complexes and cell-specific transcription activators during development and differentiation.
机译：由通用转录因子（GTF）组成的功能性预启动复合物（PIC）的有序组装是RNA聚合酶II转录蛋白质编码基因的前提。由TATA结合蛋白（TBP）和13个TBP相关因子（TAF）组成的TFIID是一种GTF，被认为可以识别允许位点特异性PIC组装的启动子序列。转录辅助因子（例如SAGA）对于严格调节转录起始也是必需的。两种含TAF10的复合物（TFIID，SAGA）对红细胞生成的贡献仍然难以捉摸。通过在体内红细胞中特异性地消融TAF10，我们观察到分化障碍伴随着失活的GATA1靶基因，包括 Gata1 本身，暗示了GATA1与TAF10之间的功能性串扰。此外，我们通过质谱分析了小鼠和人类细胞中TFIID和SAGA复合物的组成，发现在类红细胞分化和发育过程中，它们的整体完整性得以保持，并且有微小的变化。与我们的功能数据一致，我们表明TAF10与GATA1直接相互作用，并且TAF10在人胎儿红系细胞的 GATA1 基因座中富集。因此，我们的发现表明，在发育和分化过程中，规范性TFIID和SAGA复合物与细胞特异性转录激活因子之间存在相互影响。

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