Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes
Witzel M, Petersheim D, Fan Y, Bahrami E, Racek T, Rohlfs M, Puchalka J, Mertes C, Gagneur J, Ziegenhain C, Enard W, Stray-Pedersen A, Arkwright PD, Abboud MR, Pazhakh V, Lieschke GJ, Krawitz PM, Dahlhoff M, Schneider MR, Wolf E, Horny HP, Schmidt H, Schaffer AA, Klein C (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 49
Pages Range: 742-752
Journal Issue: 5
DOI: 10.1038/ng.3833
Abstract
We identify SMARCD2 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily D, member 2), also known as BAF60b (BRG1/Brahma-associated factor 60b), as a critical regulator of myeloid differentiation in humans, mice, and zebrafish. Studying patients from three unrelated pedigrees characterized by neutropenia, specific granule deficiency, myelodysplasia with excess of blast cells, and various developmental aberrations, we identified three homozygous loss-of-function mutations in SMARCD2. Using mice and zebrafish as model systems, we showed that SMARCD2 controls early steps in the differentiation of myeloid-erythroid progenitor cells. In vitro, SMARCD2 interacts with the transcription factor CEBPIϵ and controls expression of neutrophil proteins stored in specific granules. Defective expression of SMARCD2 leads to transcriptional and chromatin changes in acute myeloid leukemia (AML) human promyelocytic cells. In summary, SMARCD2 is a key factor controlling myelopoiesis and is a potential tumor suppressor in leukemia.
Involved external institutions
Ludwig-Maximilians-Universität (LMU)
Germany (DE)
Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet
Norway (NO)
University of Manchester
United Kingdom (GB)
American University of Beirut (AUB) / الجامعة الأميركية في بيروت
Lebanon (LB)
Monash University
Australia (AU)
Charité - Universitätsmedizin Berlin
Germany (DE)
US National Institutes of Health (NIH)
United States (USA) (US)
Germany (DE)
Oslo University Hospital / Oslo Universitetssykehus Rikshospitalet
Norway (NO)
University of Manchester
United Kingdom (GB)
American University of Beirut (AUB) / الجامعة الأميركية في بيروت
Lebanon (LB)
Monash University
Australia (AU)
Charité - Universitätsmedizin Berlin
Germany (DE)
US National Institutes of Health (NIH)
United States (USA) (US)
How to cite
APA:
Witzel, M., Petersheim, D., Fan, Y., Bahrami, E., Racek, T., Rohlfs, M.,... Klein, C. (2017). Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes. Nature Genetics, 49(5), 742-752. https://doi.org/10.1038/ng.3833
MLA:
Witzel, Maximilian, et al. "Chromatin-remodeling factor SMARCD2 regulates transcriptional networks controlling differentiation of neutrophil granulocytes." Nature Genetics 49.5 (2017): 742-752.
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