Proteomic and functional analyses reveal the role of chromatin reader SFMBT1 in regulating epigenetic silencing and the myogenic gene program.
SFMBT1 belongs to the malignant brain tumor domain-containing chromatin reader family that recognizes repressive histone marks and represses transcription. The biological functions and molecular basis underlying SFMBT1-mediated transcriptional repression are poorly elucidated. Here, our proteomic analysis revealed that SFMBT1 is associated with multiple transcriptional corepressor complexes, including CtBP/LSD1/HDAC complexes, polycomb repressive complexes, and malignant brain tumor family proteins, that collectively contribute to SFMBT1 repressor activity. During myogenesis, Sfmbt1 represses myogenic differentiation of cultured and primary myoblasts. Mechanistically, Sfmbt1 interacts with MyoD and mediates epigenetic silencing of MyoD target genes via recruitment of its associated corepressors and subsequent induction of epigenetic modifications and chromatin compaction. Therefore, our study identified novel mechanisms accounting for SFMBT1-mediated transcription repression and revealed an essential role of Sfmbt1 in regulating MyoD-mediated transcriptional silencing that is required for the maintenance of undifferentiated states of myogenic progenitor cells.
Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA.
Shuibin
S
Lin
Huangxuan
H
Shen
Jian-Liang
JL
Li
Shaojun
S
Tang
Yumei
Y
Gu
Zirong
Z
Chen
Chengbin
C
Hu
Judd C
JC
Rice
Jianrong
J
Lu
Lizi
L
Wu
D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D020868:Gene Silencing / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D056466:Histone Demethylases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D024510:Muscle Development / Q000502:physiology*; D017570:MyoD Protein / Q000235:genetics / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000502:physiology*
D017570:MyoD Protein; C057363:MyoD1 myogenic differentiation protein; D012097:Repressor Proteins; C523369:SFMBT1 protein, human; D056466:Histone Demethylases; C495195:KDM1A protein, human; D006655:Histone Deacetylases