@article{d575f81816094874b477a4eff2b981ed,
title = "Asxl1 deletion disrupts MYC and RNA polymerase II function in granulocyte progenitors",
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 Asxl1 deletion. In granulocyte progenitors, Asxl1 deletion 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, Asxl1 deletion 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.",
author = "Braun, {Theodore P.} and Joseph Estabrook and Zachary Schonrock and Curtiss, {Brittany M.} and Lucie Darmusey and Jommel Macaraeg and Trevor Enright and Cody Coblentz and Rowan Callahan and William Yashar and Akram Taherinasab and Hisham Mohammed and Coleman, {Daniel J.} and Druker, {Brian J.} and Emek Demir and Lusardi, {Theresa A.} and Maxson, {Julia E.}",
note = "Funding Information: We would like to thank Dr. Marilynn Chow-Castro for her thoughtful discussions and Hannah Manning for her contributions related to the Causal Path analysis; the OHSU Massively Parallel Sequencing Shared Resource for scRNA-seq library prep using their 10X Genomics Chromium Controller and performing short read sequencing assays. This project was supported by funding from the Cancer Early Detection and Research center (CEDAR) at Oregon Health and Science University{\textquoteright}s Knight Cancer Institute, funding from the Edward P. Evans Foundation to TPB and R01HL157147 from the NCI to JEM. Funding Information: We would like to thank Dr. Marilynn Chow-Castro for her thoughtful discussions and Hannah Manning for her contributions related to the Causal Path analysis; the OHSU Massively Parallel Sequencing Shared Resource for scRNA-seq library prep using their 10X Genomics Chromium Controller and performing short read sequencing assays. This project was supported by funding from the Cancer Early Detection and Research center (CEDAR) at Oregon Health and Science University{\textquoteright}s Knight Cancer Institute, funding from the Edward P. Evans Foundation to TPB and R01HL157147 from the NCI to JEM. Publisher Copyright: {\textcopyright} 2022, The Author(s), under exclusive licence to Springer Nature Limited.",
year = "2023",
month = feb,
doi = "10.1038/s41375-022-01792-x",
language = "English (US)",
volume = "37",
pages = "478--487",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",
number = "2",
}