학술논문
Asxl1deletion disrupts MYC and RNA polymerase II function in granulocyte progenitors
Document Type
Article
Author
Braun, Theodore P.; Estabrook, Joseph; Schonrock, Zachary; Curtiss, Brittany M.; Darmusey, Lucie; Macaraeg, Jommel; Enright, Trevor; Coblentz, Cody; Callahan, Rowan; Yashar, William; Taherinasab, Akram; Mohammed, Hisham; Coleman, Daniel J.; Druker, Brian J.; Demir, Emek; Lusardi, Theresa A.; Maxson, Julia E.
Source
Leukemia; February 2023, Vol. 37 Issue: 2 p478-487, 10p
Subject
Language
ISSN
08876924; 14765551
Abstract
Mutations in the gene Additional Sex-Combs Like 1(ASXL1) are recurrent in myeloid malignancies as well as the pre-malignant condition clonal hematopoiesis, where they are universally associated with poor prognosis. However, the role of ASXL1 in myeloid lineage maturation is incompletely described. To define the role of ASXL1 in myelopoiesis, we employed single cell RNA sequencing and a murine model of hematopoietic-specific Asxl1deletion. In granulocyte progenitors, Asxl1deletion leads to hyperactivation of MYC and a quantitative decrease in neutrophil production. This loss of granulocyte production was not accompanied by significant changes in the landscape of covalent histone modifications. However, Asxl1deletion results in a decrease in RNAPII promoter-proximal pausing in granulocyte progenitors, indicative of a global increase in productive transcription. These results suggest that ASXL1 inhibits productive transcription in granulocyte progenitors, identifying a new role for this epigenetic regulator in myeloid development.