Witzel M
; Petersheim D
; Fan Y
; Bahrami E
; Racek T
; Rohlfs M
; Pucha?ka 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
; Schäffer AA
; Klein C
Nat Genet
2017[May]; 49
(5
): 742-752
PMID28369036
show ga
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 CEBP? 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.
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