GATA1 and PU.1 Bind to Ribosomal Protein Genes in Erythroid Cells: Implications for Ribosomopathies.
GATA1 and PU.1 Bind to Ribosomal Protein Genes in Erythroid Cells: Implications for Ribosomopathies.
复制标题
DOI：
10.1371/journal.pone.0140077
复制
发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Vizirianakis IS
中科院分区：
文献类型：
--
作者：
Amanatiadou EP;Papadopoulos GL;Strouboulis J;Vizirianakis IS
核糖体生物发生功能障碍与特定造血相关疾病之间的明确联系促使我们研究关键谱系特异性转录因子在红细胞终末分化期间核糖体蛋白（RP）基因转录调节中的作用。通过在小鼠红白血病细胞中应用EMSA和ChIP方法，我们表明GATA 1和PU.1在体外和体内结合RPS 19基因的近端启动子区域，该基因在Diamond-Blackfan贫血中经常突变。此外，ChIPseq数据分析还表明，在小鼠和人红系细胞中，几种RP基因富集为潜在的GATA 1和PU.1基因靶标，GATA 1结合显示出与人和小鼠终末红系分化期间较高的核糖体蛋白基因表达水平相关。我们的研究结果表明，RP基因的表达，因此平衡的核糖体生物合成可能是特定的和选择性的调节谱系特异性转录因子在造血过程中，这一发现可能是临床相关的核糖体病。
The clear connection between ribosome biogenesis dysfunction and specific hematopoiesis-related disorders prompted us to examine the role of critical lineage-specific transcription factors in the transcriptional regulation of ribosomal protein (RP) genes during terminal erythroid differentiation. By applying EMSA and ChIP methodologies in mouse erythroleukemia cells we show that GATA1 and PU.1 bind in vitro and in vivo the proximal promoter region of the RPS19 gene which is frequently mutated in Diamond-Blackfan Anemia. Moreover, ChIPseq data analysis also demonstrates that several RP genes are enriched as potential GATA1 and PU.1 gene targets in mouse and human erythroid cells, with GATA1 binding showing an association with higher ribosomal protein gene expression levels during terminal erythroid differentiation in human and mouse. Our results suggest that RP gene expression and hence balanced ribosome biosynthesis may be specifically and selectively regulated by lineage specific transcription factors during hematopoiesis, a finding which may be clinically relevant to ribosomopathies.