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Genome-Wide Organization of GATA1 and TAL1 Determined at High Resolution

机译:高分辨率确定了GATA1和TAL1的基因组范围

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Erythroid development and differentiation from multiprogenitor cells into red blood cells requires precise transcriptional regulation. Key erythroid transcription factors, GATA1 and TAL1, cooperate, along with other proteins, to regulate many aspects of this process. How GATA1 and TAL1 are juxtaposed along the DNA and their cognate DNA binding site across the mouse genome remains unclear. We applied high-resolution ChIP-exo (chromatin immunoprecipitation followed by 5′-to-3′ exonuclease treatment and then massively parallel DNA sequencing) to GATA1 and TAL1 to study their positional organization across the mouse genome during GATA1-dependent maturation. Two complementary methods, MultiGPS and peak pairing, were used to determine high-confidence binding locations by ChIP-exo. We identified ~10,000 GATA1 and ~15,000 TAL1 locations, which were essentially confirmed by ChIP-seq (chromatin immunoprecipitation followed by massively parallel DNA sequencing). Of these, ~4,000 locations were bound by both GATA1 and TAL1. About three-quarters of them were tightly linked to a partial E-box located 7 or 8 bp upstream of a WGATAA motif. Both TAL1 and GATA1 generated distinct characteristic ChIP-exo peaks around WGATAA motifs that reflect their positional arrangement within a complex. We show that TAL1 and GATA1 form a precisely organized complex at a compound motif consisting of a TG 7 or 8 bp upstream of a WGATAA motif across thousands of genomic locations.
机译:红细胞的发育和从多祖细胞分化为红细胞的过程需要精确的转录调控。关键的类红细胞转录因子GATA1和TAL1与其他蛋白质一起调节该过程的许多方面。目前尚不清楚如何将GATA1和TAL1沿DNA并置并排列在小鼠基因组上的同源DNA结合位点。我们对GATA1和TAL1应用了高分辨率ChIP-exo(染色质免疫沉淀,然后进行5'至3'核酸外切酶处理,然后大规模平行DNA测序),以研究它们在GATA1依赖性成熟过程中在小鼠基因组中的位置组织。两种互补的方法,MultiGPS和峰配对,用于通过ChIP-exo确定高可信度的结合位置。我们确定了大约10,000个GATA1和大约15,000个TAL1位置,这些位置基本上由ChIP-seq(染色质免疫沉淀,然后大规模平行DNA测序)确认。其中,约4,000个位置受GATA1和TAL1的约束。其中约四分之三与WGATAA基序上游7或8 bp的部分E-box紧密连接。 TAL1和GATA1都在WGATAA图案周围生成了不同的特征性ChIP-exo峰,反映了它们在复合物中的位置。我们显示,TAL1和GATA1在由TGATAA主题的TG 7或8 bp上游跨数千个基因组位置的TG 7或8 bp组成的复合主题上形成了精确组织的复合物。

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