SATB1 chromatin loops regulate Megakaryocyte/Erythroid Progenitor Expansion by facilitating HSP70 and GATA1 induction.
Mark C WilkesHee-Don ChaeVanessa ScanlonAlma-Martina CepikaEthan P WentworthMallika SaxenaAscia EskinZugen ChenBert GladerMaria Grazia RoncaroloStanley F NelsonKathleen M SakamotoPublished in: Stem cells (Dayton, Ohio) (2023)
Diamond Blackfan Anemia (DBA) is an inherited bone marrow failure syndrome associated with severe anemia, congenital malformations and increased risk of developing cancer. The chromatin-binding 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 HSP70 and GATA1 that accompanies MEP differentiation. SATB1 binding to specific sites surrounding the HSP70 genes, promotes chromatin loops that are required for 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.
Keyphrases
- transcription factor
- heat shock protein
- heat shock
- bone marrow
- heat stress
- chronic kidney disease
- end stage renal disease
- genome wide
- dna damage
- gene expression
- dna binding
- poor prognosis
- genome wide identification
- newly diagnosed
- single cell
- ejection fraction
- papillary thyroid
- mesenchymal stem cells
- binding protein
- cell proliferation
- dendritic cells
- acute myeloid leukemia
- early onset
- cell therapy
- long non coding rna
- sensitive detection
- stem cells
- lymph node metastasis
- immune response
- patient reported
- young adults
- signaling pathway
- patient reported outcomes