MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm.
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
received:
06
09
2019
accepted:
28
01
2021
revised:
22
01
2021
pubmed:
6
3
2021
medline:
5
3
2022
entrez:
5
3
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33664480
doi: 10.1038/s41418-021-00744-9
pii: 10.1038/s41418-021-00744-9
pmc: PMC8257666
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Hepatocyte Nuclear Factor 1-alpha
0
Hnf1a protein, mouse
0
Macf1 protein, mouse
0
Microfilament Proteins
0
Tcf12 protein, mouse
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2160-2178Subventions
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 31570940, 82072106
Organisme : National Natural Science Foundation of China (National Science Foundation of China)
ID : 81772017
Organisme : China Postdoctoral Science Foundation
ID : 2018T111099, 2017M610653
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