GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma

Natsumeda, Manabu; Miyahara, Hiroaki; Yoshimura, Junichi; Nakata, Satoshi; Nozawa, Takanori; Itô, Junko; Kang, Yu; Watanabe, Jun; Tsukamoto, Yoshihiro; Okada, Masayasu; Oishi, Makoto; Hirato, Junko; Wataya, Takafumi; Ahsan, Sama; Tateishi, Kensuke; Yamamoto, Tetsuya; Rodríguez, Fausto J.; Takahashi, Hitoshi; Hovestadt, Volker; Suvà, Mario L.; Taylor, Michael D.; Eberhart, Charles G.; Fujii, Yukihiko; Kakita, Akiyoshi

doi:10.1093/jnen/nlaa141

Cited by 5 publications

(3 citation statements)

References 24 publications

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“…Like zinc finger protein with KRAB and SCAN domains 3 (ZKSCAN3) from C2H2 type, downregulation of ZKSCAN3 is observed in aged human mesenchymal stem cells (hMSCs) and depletion of ZKSCAN3 accelerates senescence of these cells ( Hu et al, 2020 ; Turelli et al, 2020 ). ZNF also play an important role in brain tumor disease ( Balogh et al, 2020 ; Liang et al, 2020 ; Natsumeda et al, 2021 ; Okado, 2021 ). The AN1/A20 zinc finger domain containing protein 3 (ZFAND3) as a crucial driver of glioblastoma invasion.…”

Section: Discussionmentioning

confidence: 99%

Zinc Finger Proteins in Neuro-Related Diseases Progression

Liu

et al. 2021

Front. Neurosci.

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Zinc finger proteins (ZNF) are among the most abundant proteins in eukaryotic genomes. It contains several zinc finger domains that can selectively bind to certain DNA or RNA and associate with proteins, therefore, ZNF can regulate gene expression at the transcriptional and translational levels. In terms of neurological diseases, numerous studies have shown that many ZNF are associated with neurological diseases. The purpose of this review is to summarize the types and roles of ZNF in neuropsychiatric disorders. We will describe the structure and classification of ZNF, then focus on the pathophysiological role of ZNF in neuro-related diseases and summarize the mechanism of action of ZNF in neuro-related diseases.

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Section: Discussionmentioning

confidence: 99%

Zinc Finger Proteins in Neuro-Related Diseases Progression

Liu

et al. 2021

Front. Neurosci.

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“…A similar analysis for adult chondrocytes showed enrichment for GATA1, RELB, IRF6, SMAD3, TWIST2, and other binding motifs. Although the role of these genes in chondrocytes is not completely clear, these transcription factors are known to be essential for differentiation and lineage commitment in different cell types (Alvisi et al, 2020 ; Kitajima et al, 2006 ; Natsumeda et al, 2021 ). For OA chondrocytes, we obtained a DNA motif for NF–kB, which is a well‐known transcription factor that mediates inflammation.…”

Section: Resultsmentioning

confidence: 99%

STAT3 promotes a youthful epigenetic state in articular chondrocytes

et al. 2023

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Epigenetic mechanisms guiding articular cartilage regeneration and age‐related disease such as osteoarthritis (OA) are poorly understood. STAT3 is a critical age‐patterned transcription factor highly active in fetal and OA chondrocytes, but the context‐specific role of STAT3 in regulating the epigenome of cartilage cells remain elusive. In this study, DNA methylation profiling was performed across human chondrocyte ontogeny to build an epigenetic clock and establish an association between CpG methylation and human chondrocyte age. Exposure of adult chondrocytes to a small molecule STAT3 agonist decreased DNA methylation, while genetic ablation of STAT3 in fetal chondrocytes induced global hypermethylation. CUT&RUN assay and subsequent transcriptional validation revealed DNA methyltransferase 3 beta (DNMT3B) as one of the putative STAT3 targets in chondrocyte development and OA. Functional assessment of human OA chondrocytes showed the acquisition of progenitor‐like immature phenotype by a significant subset of cells. Finally, conditional deletion of Stat3 in cartilage cells increased DNMT3B expression in articular chondrocytes in the knee joint in vivo and resulted in a more prominent OA progression in a post‐traumatic OA (PTOA) mouse model induced by destabilization of the medial meniscus (DMM). Taken together these data reveal a novel role for STAT3 in regulating DNA methylation in cartilage development and disease. Our findings also suggest that elevated levels of active STAT3 in OA chondrocytes may indicate an intrinsic attempt of the tissue to regenerate by promoting a progenitor‐like phenotype. However, it is likely that chronic activation of this pathway, induced by IL‐6 cytokines, is detrimental and leads to tissue degeneration.

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“…Although the role of these genes in chondrocytes remains unclear, these transcription factors are known to be essential for differentiation and lineage commitment in different cell types [41][42][43][44][45] . To date, researchers have uncovered several STAT3 binding targets across various other tissues and cell types.…”

Section: Genome-wide Putative Stat3 Targets Differ In Development and Diseasementioning

confidence: 99%

Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes

Sarkar

Lee

Shkhyan

et al. 2021

Preprint

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Articular chondrocytes undergo functional changes and their regenerative potential declines with age. Although the molecular mechanisms guiding articular cartilage aging is poorly understood, DNA methylation is known to play a mechanistic role in aging. However, our understanding of DNA methylation in chondrocyte development across human ontogeny is limited. To better understand DNA methylome changes, methylation profiling was performed in human chondrocytes. This study reveals association between methylation of specific CpG sites and chondrocyte age. We also determined the putative binding targets of STAT3, a key age–patterned transcription factor in fetal chondrocytes and genetic ablation of STAT3 induced a global genomic hypermethylation. Moreover, an epigenetic clock built for adult human chondrocytes revealed that exposure of aged adult human chondrocytes to STAT3 agonist, decreased epigenetic age. Taken together, this work will serve as a foundation to understand development and aging of chondrocytes with a new perspective for development of rejuvenation agents for synovial joints.

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GLI3 Is Associated With Neuronal Differentiation in SHH-Activated and WNT-Activated Medulloblastoma

Cited by 5 publications

References 24 publications

Zinc Finger Proteins in Neuro-Related Diseases Progression

Zinc Finger Proteins in Neuro-Related Diseases Progression

STAT3 promotes a youthful epigenetic state in articular chondrocytes

Genome-wide DNA methylation and multi-omics study of human chondrocyte ontogeny and an epigenetic clock analysis of adult chondrocytes

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