SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.
SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.
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SATB1 染色质环通过促进 HSP70 和 GATA1 诱导来调节巨核细胞/红系祖细胞扩增。
DOI：
10.1093/stmcls/sxad025
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Sakamoto,KathleenM
中科院分区：
文献类型：
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作者：
Wilkes,MarkC;Chae,Hee-Don;Scanlon,Vanessa;Cepika,Alma-Martina;Wentworth,EthanP;Saxena,Mallika;Eskin,Ascia;Chen,Zugen;Glader,Bert;GraziaRoncarolo,Maria;Nelson,StanleyF;Sakamoto,KathleenM
戴蒙德·布莱克范贫血 (DBA) 是一种遗传性骨髓衰竭综合征，与严重贫血、先天性畸形和患癌症风险增加相关。 DBA 患者和细胞模型的巨核细胞/红系祖细胞 (MEP) 中染色质结合的特殊 AT 序列结合蛋白 (SATB1) 下调，导致 MEP 扩增减少。在这里，我们证明 SATB1 表达是伴随 MEP 分化的关键红细胞因子热休克蛋白 70 (HSP70) 和 GATA1 上调所必需的。 SATB1 与 HSP70 基因周围特定位点的结合会促进诱导 HSP70 所需的染色质环，进而促进 GATA1 的诱导。这表明 SATB1 虽然在骨髓生成过程中逐渐下调，但在早期骨髓祖细胞中保持了生物学功能。
Diamond Blackfan anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations, and an increased risk of developing cancer. The chromatin-binding special AT-rich sequence-binding protein-1 (SATB1) is downregulated in megakaryocyte/erythroid progenitors (MEPs) in patients and cell models of DBA, leading to a reduction in MEP expansion. Here we demonstrate that SATB1 expression is required for the upregulation of the critical erythroid factors heat shock protein 70 (HSP70) and GATA1 which accompanies MEP differentiation. SATB1 binding to specific sites surrounding the HSP70 genes promotes chromatin loops that are required for the induction of HSP70, which, in turn, promotes GATA1 induction. This demonstrates that SATB1, although gradually downregulated during myelopoiesis, maintains a biological function in early myeloid progenitors.