Department of Molecular Genetics and Microbiology, Shands Cancer Center, University of Florida, Gainesville, Florida 32610, USA.
J Biol Chem. 2013 Mar 1;288(9):6238-47. doi: 10.1074/jbc.M112.429605. Epub 2013 Jan 24.
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.
SFMBT1 属于恶性脑肿瘤结构域包含染色质读取器家族，可识别抑制性组蛋白标记并抑制转录。SFMBT1 介导的转录抑制的生物学功能和分子基础尚未得到充分阐明。在这里，我们的蛋白质组学分析表明，SFMBT1 与多种转录共抑制复合物相关，包括 CtBP/LSD1/HDAC 复合物、多梳抑制复合物和恶性脑肿瘤家族蛋白，它们共同有助于 SFMBT1 抑制活性。在成肌分化过程中，Sfmbt1 抑制培养的和原代成肌细胞的成肌分化。在机制上，Sfmbt1 与 MyoD 相互作用，并通过募集其相关的共抑制因子，以及随后诱导表观遗传修饰和染色质紧缩，介导 MyoD 靶基因的表观遗传沉默。因此，我们的研究确定了 SFMBT1 介导的转录抑制的新机制，并揭示了 Sfmbt1 在调节 MyoD 介导的转录沉默中的重要作用，这对于维持成肌祖细胞的未分化状态是必需的。
