SATB1 Chromatin Loops Regulate Megakaryocyte/Erythroid Progenitor Expansion by Facilitating HSP70 and GATA1 Induction.

Autor: Wilkes MC; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA., Chae HD; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA., Scanlon V; Department of Laboratory Medicine, Yale Stem Cell Center, Yale Cooperative Center of Excellence in Hematology, Yale School of Medicine, New Haven, CT, USA., Cepika AM; Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Wentworth EP; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA., Saxena M; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA., Eskin A; Department of Pathology and Laboratory Medicine¸ David Geffen School of Medicine, University of California, Los Angeles, CA, USA., Chen Z; Department of Pathology and Laboratory Medicine¸ David Geffen School of Medicine, University of California, Los Angeles, CA, USA., Glader B; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA., Grazia Roncarolo M; Institute for Stem Cell Biology and Regenerative Medicine, Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA., Nelson SF; Department of Pathology and Laboratory Medicine¸ David Geffen School of Medicine, University of California, Los Angeles, CA, USA., Sakamoto KM; Division of Hematology/Oncology, Department of Pediatrics, Stanford University, Stanford, CA, USA.
Jazyk: angličtina
Zdroj: Stem cells (Dayton, Ohio) [Stem Cells] 2023 Jun 15; Vol. 41 (6), pp. 560-569.
DOI: 10.1093/stmcls/sxad025
Abstrakt: 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.
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Databáze: MEDLINE