MACF1 Promotes Osteoblast Differentiation by Sequestering Wnt Signaling Repressors in Cytoplasm [RNA-seq]
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PROVIDER: PRJNA492300 | ENA |
REPOSITORIES: ENA
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Project description:MACF1 promotes osteoblast differentiation by sequestering repressors in cytoplasm
| PRJNA492304 | ENA
Project description:MACF1 Promotes Osteoblast Differentiation by Sequestering Wnt Signaling Repressors in Cytoplasm [ChIP-seq]
| PRJNA492306 | ENA
Project description:Osteoblast differentiation leading to bone formation requires a coordinated transcriptional program. We have recently demonstrated that microtubule actin crosslinking factor 1 (MACF1) promotes osteoblast differentiation, suggesting a key role in regulating early-phase osteoblast differentiation. Here, we showed that the early-phase osteoblast differentiation transcriptome dynamics was regulated by MACF1 and the transcription of TCF7/LEF1, key effectors of Wnt signaling that is important for osteoblast differentiation was suppressed by MACF1 knockdown. Co-IP and Protein mass spectrometry revealed that MACF1 interacted with a known and two previously unknown repressors of TCF7/LEF1, DKK1, CDK12 and MEAF6. ChIP-seq analysis of MACF1-associated promoters further revealed that MACF1 interacted with transcription factors TCF12 and E2F6, which also suppressed the transcription of TCF7/LEF1. Furthermore, all these four MACF-interacted proteins inhibited osteoblast differentiation. By studying the underlying mechanism, we found that cytoplasmic-nuclear localization of MACF1 was dependent on its level and the cytoplasmic-nuclear localization of TCF12 and E2F6 was regulated by MACF1 localization. In addition, MACF1 oppositely regulated the transcription activity of TCF12 and TCF7. Current study, for the first time to our knowledge, suggest that MACF1 acts as a sponge of osteoblast differentiation repressors to promote osteoblast differentiation, and indicate a novel mechanism for regulating the cellular location of transcription factors by a protein associated with microtubule and actin.
2021-02-17 | GSE120251 | GEO
Project description:Osteoblast differentiation leading to bone formation requires a coordinated transcriptional program. We have recently demonstrated that microtubule actin crosslinking factor 1 (MACF1) promotes osteoblast differentiation, suggesting a key role in regulating early-phase osteoblast differentiation. Here, we showed that the early-phase osteoblast differentiation transcriptome dynamics was regulated by MACF1 and the transcription of TCF7/LEF1, key effectors of Wnt signaling that is important for osteoblast differentiation was suppressed by MACF1 knockdown. Co-IP and Protein mass spectrometry revealed that MACF1 interacted with a known and two previously unknown repressors of TCF7/LEF1, DKK1, CDK12 and MEAF6. ChIP-seq analysis of MACF1-associated promoters further revealed that MACF1 interacted with transcription factors TCF12 and E2F6, which also suppressed the transcription of TCF7/LEF1. Furthermore, all these four MACF-interacted proteins inhibited osteoblast differentiation. By studying the underlying mechanism, we found that cytoplasmic-nuclear localization of MACF1 was dependent on its level and the cytoplasmic-nuclear localization of TCF12 and E2F6 was regulated by MACF1 localization. In addition, MACF1 oppositely regulated the transcription activity of TCF12 and TCF7. Current study, for the first time to our knowledge, suggest that MACF1 acts as a sponge of osteoblast differentiation repressors to promote osteoblast differentiation, and indicate a novel mechanism for regulating the cellular location of transcription factors by a protein associated with microtubule and actin.
2021-02-17 | GSE120248 | GEO
Project description: Not available
| S-EPMC8257666 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2021-02-17 | GSE120252 | GEO
Project description:METTL16 was previously identified as an m6A methyltransferase. In this study, we validated the cytoplasmic location of METTL16 and explored its function in the cytoplasm. We found that METTL16 promoted translation by sequestering eIF4E2, a translation initiation repressor, from the 5' cap structure.
2022-03-07 | GSE197915 | GEO
Project description:Background: Osteoblast differentiation requires the coordinated stepwise expression of multiple genes. Histone deacetylase inhibitors (HDIs) accelerate the osteoblast differentiation process by blocking the activity of histone deacetylases (HDACs), which alter gene expression by modifying chromatin structure. We previously demonstrated that HDIs and HDAC3 shRNAs accelerate matrix mineralization and the expression of osteoblast maturation genes (e.g. alkaline phosphatase, osteocalcin). Identifying other genes that are differentially regulated by HDIs might identify new pathways that contribute to osteoblast differentiation. Results: To identify other osteoblast genes that are altered early by HDIs, we incubated MC3T3-E1 preosteoblasts with HDIs (trichostatin A, MS-275, or valproic acid) for 18 hours in osteogenic conditions. The promotion of osteoblast differentiation by HDIs in this experiment was confirmed by osteogenic assays. Gene expression profiles relative to vehicle-treated cells were assessed by microarray analysis with Affymetrix GeneChip 430 2.0 arrays. The regulation of several genes by HDIs in MC3T3-E1 cells and primary osteoblasts was verified by quantitative real-time PCR. Nine genes were differentially regulated by at least two-fold after exposure to each of the three HDIs and six were verified by PCR in osteoblasts. Four of the verified genes (solute carrier family 9 isoform 3 regulator 1 (Slc9a3r1), sorbitol dehydrogenase 1, a kinase anchor protein, and glutathione S-transferase alpha 4) were induced. Two genes (proteasome subunit, beta type 10 and adaptor-related protein complex AP-4 sigma 1) were suppressed. We also identified eight growth factors and growth factor receptor genes that are significantly altered by each of the HDIs, including Frizzled related proteins 1 and 4, which modulate the Wnt signaling pathway. Conclusions: This study identifies osteoblast genes that are regulated early by HDIs and indicates pathways that might promote osteoblast maturation following HDI exposure. One gene whose upregulation following HDI treatment is consistent with this notion is Slc9a3r1. Also known as NHERF1, Slc9a3r1 is required for optimal bone density. Similarly, the regulation of Wnt receptor genes indicates that this crucial pathway in osteoblast development is also affected by HDIs. These data support the hypothesis that HDIs regulate the expression of genes that promote osteoblast differentiation and maturation. Keywords: gene expression
2007-10-06 | GSE9247 | GEO
Project description:Global expression profile of human osteoblast treated with melphalen, compared to human osteoblast cells treated with diluent control
2010-09-30 | GSE17839 | GEO
Project description:Cell proliferation is tightly controlled by inhibitors that block cell cycle progression until growth signals relieve this inhibition, allowing cells to divide. In several tissues including the liver, cell proliferation is inhibited at mitosis by the transcriptional repressors E2F7 and E2F8, leading to formation of polyploid cells. Whether growth factors promote mitosis and cell cycle progression by relieving the E2F7/E2F8-mediated inhibition is unknown. We report here on a new mechanism of cell division control in the postnatal liver, in which Wnt/βcatenin signaling maintains active hepatocyte cell division through Tbx3, a Wnt target gene. Tbx3 directly represses transcription of E2F7 and E2F8, thereby promoting mitosis. This cascade of sequential transcriptional repressors, initiated by Wnt signals, provides a new paradigm for exploring how commonly active developmental signals impact cell cycle completion.
2022-07-02 | GSE205339 | GEO