Metabolism of Model Microorganisms, Labiris, Brussels, Belgium.
Laboratoire de Microbiologie, Université Libre de Bruxelles, Brussels, Belgium.
PLoS Genet. 2019 Feb 28;15(2):e1007999. doi: 10.1371/journal.pgen.1007999. eCollection 2019 Feb.
GATA transcription factors are highly conserved among eukaryotes and play roles in transcription of genes implicated in cancer progression and hematopoiesis. However, although their consensus binding sites have been well defined in vitro, the in vivo selectivity for recognition by GATA factors remains poorly characterized. Using ChIP-Seq, we identified the Dal80 GATA factor targets in yeast. Our data reveal Dal80 binding to a large set of promoters, sometimes independently of GATA sites, correlating with nitrogen- and/or Dal80-sensitive gene expression. Strikingly, Dal80 was also detected across the body of promoter-bound genes, correlating with high expression. Mechanistic single-gene experiments showed that Dal80 spreading across gene bodies requires active transcription. Consistently, Dal80 co-immunoprecipitated with the initiating and post-initiation forms of RNA Polymerase II. Our work suggests that GATA factors could play dual, synergistic roles during transcription initiation and post-initiation steps, promoting efficient remodeling of the gene expression program in response to environmental changes.
GATA 转录因子在真核生物中高度保守,在涉及癌症进展和造血的基因转录中发挥作用。然而,尽管它们的共识结合位点在体外得到了很好的定义,但 GATA 因子的体内识别选择性仍未得到很好的描述。我们使用 ChIP-Seq 鉴定了酵母中的 Dal80 GATA 因子靶标。我们的数据显示 Dal80 与一组大的启动子结合,有时独立于 GATA 位点,与氮和/或 Dal80 敏感基因表达相关。引人注目的是,Dal80 也在启动子结合基因的主体上被检测到,与高表达相关。机制性单基因实验表明,Dal80 在基因主体上的扩散需要活跃的转录。一致地,Dal80 与起始和起始后 RNA 聚合酶 II 的形式共免疫沉淀。我们的工作表明,GATA 因子在转录起始和起始后步骤中可能发挥双重协同作用,促进基因表达程序在应对环境变化时的有效重塑。