MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm
Autor: | Zhihao Chen, Dong Chen, Qian Airong, Lifang Hu, Shuyu Liu, Yu Zhang, Zizhan Huang, Xia Xu, Yi Zhang, Zixiang Wu, Shujing Liang, Chong Yin |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
Cytoplasm Repressor Article Cell Line Transcriptome Mice 03 medical and health sciences 0302 clinical medicine Osteogenesis Transcription (biology) Basic Helix-Loop-Helix Transcription Factors medicine Animals Hepatocyte Nuclear Factor 1-alpha E2F education Molecular Biology Transcription factor education.field_of_study Osteoblasts Chemistry Microfilament Proteins Transcription Factor 7 Cell Differentiation Osteoblast Cell Biology Cell biology 030104 developmental biology medicine.anatomical_structure MACF1 030220 oncology & carcinogenesis Signal Transduction |
Zdroj: | Cell Death Differ |
ISSN: | 1476-5403 1350-9047 |
Popis: | Osteoblast differentiation leading to bone formation requires a coordinated transcriptional program. Osteoblastic cells with low level of microtubule actin crosslinking factor 1 (MACF1) show reduced osteoblast differentiation ability, however, the comprehensive mechanism of MACF1's action remains unexplored. In the current study, we found that MACF1 knockdown suppressed osteoblast differentiation by altering the transcriptome dynamics. We further identified two MACF1-interacted proteins, cyclin-dependent kinase 12 (CDK12) and MYST/Esa1-associated factor 6 (MEAF6), and two MACF1-interacted transcription factors (TFs), transcription factor 12 (TCF12) and E2F transcription factor 6 (E2F6), which repress osteoblast differentiation by altering the expression of osteogenic TFs and genes. Moreover, we found that MACF1 regulated cytoplasmic-nuclear localization of itself, TCF12 and E2F6 in a concentration-dependent manner. MACF1 oppositely regulates the expression of TCF12 and transcription factor 7 (TCF7), two TFs that drive osteoblast differentiation to opposite directions. This study reveals that MACF1, a cytoskeletal protein, acts as a sponge for repressors of osteoblast differentiation to promote osteoblast differentiation and contributes to a novel mechanistic insight of osteoblast differentiation and transcription dynamics. |
Databáze: | OpenAIRE |
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