4.7 Article

MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm

期刊

CELL DEATH AND DIFFERENTIATION
卷 28, 期 7, 页码 2160-2178

出版社

SPRINGERNATURE
DOI: 10.1038/s41418-021-00744-9

关键词

-

资金

  1. National Natural Science Foundation of China [81772017, 31570940, 82072106]
  2. China Postdoctoral Science Foundation [2018T111099, 2017M610653]
  3. Young Talent Fund of University Association for Science and Technology in Shaanxi, China [20170401]
  4. Natural Science Basic Research Plan in Shaanxi Province of China [2018JM3040, BKJ17J004]
  5. ABLife, Inc., Wuhan [201508001]

向作者/读者索取更多资源

MACF1 plays a crucial role in osteoblast differentiation by modulating transcriptome dynamics and interacting with various proteins that inhibit osteoblast differentiation. MACF1 regulates cytoplasmic-nuclear localization of itself and other factors, while also controlling the expression of transcription factors driving osteoblast differentiation.
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.

作者

我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。

评论

主要评分

4.7
评分不足

次要评分

新颖性
-
重要性
-
科学严谨性
-
评价这篇论文

推荐

暂无数据
暂无数据