Histone methyltransferase Setdb1 is indispensable for Meckel's cartilage development

Yahiro, Kohei; Higashihori, Norihisa; Moriyama, Keiji

doi:10.1016/j.bbrc.2016.11.128

Cited by 13 publications

(6 citation statements)

References 27 publications

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“…The SETDB1 protein belongs to the SET domain protein methyltransferase family and plays important roles in heterochromatin formation and gene expression [4]. As a H3K9 methyltransferase, the physiological function of SETDB1 has been associated with gene silencing in mammalian development [5], particularly involving heterochromatin formation [6], stem cell maintenance [7], and endogenous retrovirus genes repression [8]. In the field of oncology, SETDB1 has been observed to be deregulated in various human carcinogenesis, including colorectal cancer, lung cancer, melanoma, and BC [9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

High SET Domain Bifurcated 1 (SETDB1) Expression Predicts Poor Prognosis in Breast Carcinoma

Zhou

Tang

et al. 2020

Med Sci Monit

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Departmental sources Background: SETDB1, an H3K9-specific histone methyltransferase, plays important roles in the progression of various human cancers. However, the expression patterns and its clinical roles of SETDB1 remain elusive in breast cancer (BC). Material/Methods: The transcriptional level of SETDB1 and survival data in BC were analyzed through UALCAN, ONCOMINE, and Pan Cancer Prognostics Database. SETDB1 protein expression was assessed by immunohistochemistry (IHC) in 159 BC tissue samples. The associations between SETDB1 expression and clinical pathological characteristics of patients were analyzed. The GEO dataset GSE108656 was downloaded and analyzed to identify the differentially expressed genes (DEGs) between control and BC cells targeting interference with SETDB. The DEGs were further integrated by bioinformatics analysis to decipher the key signaling pathways and hub genes that are regulated by SETDB. Results: The public databases showed the level of SETDB1 mRNA was significantly upregulated in BC. Our IHC results demonstrated the level of SETDB1 protein was associated with tumor size (P=0.028), histopathological grading (P=0.012), lymph node metastasis (P<0.001), and TNM stage (P<0.001). High expression of SETDB1 indicated worse overall survival (P=0.015) and shorter relapse-free survival (P=0.027). The bioinformatic analysis of GSE108656 suggested that the SETDB1-related DEGs was mainly enriched in antigen processing and presentation, as well as immune networks in BC. The cytoHubba analysis suggested the top 10 hub genes were IL6,

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Section: Introductionmentioning

confidence: 99%

High SET Domain Bifurcated 1 (SETDB1) Expression Predicts Poor Prognosis in Breast Carcinoma

Zhou

Tang

et al. 2020

Med Sci Monit

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“…The loss of Setdb1 suppressed the differentiation of MSCs into osteoblasts and the further mineralization of osteoblasts [ 32 , 33 ]. In addition, Setdb1 was found to regulate chondrocyte proliferation and cartilage mineralization during Meckel’s cartilage development [ 34 ]. However, the effect of Setdb1 on osteoblast proliferation under mechanical unloading has not yet been clearly elucidated, which was extremely essential for the occurrence of bone loss.…”

Section: Discussionmentioning

confidence: 99%

Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip

Zhang

et al. 2022

Cells

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Bone loss caused by mechanical unloading is a threat to prolonged space flight and human health. Epigenetic modifications play a crucial role in varied biological processes, but the mechanism of histone modification on unloading-induced bone loss has rarely been studied. Here, we discovered for the first time that the methyltransferase Setdb1 was downregulated under the mechanical unloading both in vitro and in vivo so as to attenuate osteoblast proliferation. Furthermore, we found these interesting processes depended on the repression of Macrod2 expression triggered by Setdb1 catalyzing the formation of H3K9me3 in the promoter region. Mechanically, we revealed that Macrod2 was upregulated under mechanical unloading and suppressed osteoblast proliferation through the GSK-3β/β-catenin signaling pathway. Moreover, Atf7ip cooperatively contributed to osteoblast proliferation by changing the localization of Setdb1 under mechanical loading. In summary, this research elucidated the role of the Atf7ip/Setdb1/Macrod2 axis in osteoblast proliferation under mechanical unloading for the first time, which can be a potential protective strategy against unloading-induced bone loss.

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“…The 17q24.3 deletion contained no genes, is located upstream of SOX9 , does not overlap with previous deletions reported in CMPD, and likely affects expression of SOX9 ( Velagaleti et al 2005 ; Gordon et al 2009 ; Walters-Sen et al 2014 ). The deleted region of Chromosome 17 is a binding site for multiple transcription factors, including SETDB1 and KAP1 that interact with SOX9 in chondrogenesis and sex determination, respectively ( Peng et al 2009 ; Yahiro et al 2017 ). In silico analyses revealed no other rare genetic variant associated with CMPD (see Supplemental Table 1 ).…”

Section: Discussionmentioning

confidence: 99%

A novel association of campomelic dysplasia and hydrocephalus with an unbalanced chromosomal translocation upstream of SOX9

Antwi

Hong

Durán

et al. 2018

Cold Spring Harb Mol Case Stud

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Campomelic dysplasia is a rare skeletal dysplasia characterized by Pierre Robin sequence, craniofacial dysmorphism, shortening and angulation of long bones, tracheobronchomalacia, and occasionally sex reversal. The disease is due to mutations in SOX9 or chromosomal rearrangements involving the long arm of Chromosome 17 harboring the SOX9 locus. SOX9, a transcription factor, is indispensible in establishing and maintaining neural stem cells in the central nervous system. We present a patient with angulation of long bones and external female genitalia on prenatal ultrasound who was subsequently found to harbor the chromosomal abnormality 46, XY, t(6;17) (p21.1;q24.3) on prenatal genetic testing. Comparative genomic hybridization revealed deletions at 6p21.1 and 17q24.3, the latter being 2.3 Mb upstream of SOX9. Whole-exome sequencing did not identify pathogenic variants in SOX9, suggesting that the 17q24.3 deletion represents a translocation breakpoint farther upstream of SOX9 than previously identified. At 2 mo of age the patient developed progressive communicating ventriculomegaly and thinning of the cortical mantle without clinical signs of increased intracranial pressure. This case suggests ventriculomegaly in some cases represents not a primary impairment of cerebrospinal fluid dynamics, but an epiphenomenon driven by a genetic dysregulation of neural progenitor cell fate.

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Histone methyltransferase Setdb1 is indispensable for Meckel's cartilage development

Cited by 13 publications

References 27 publications

High SET Domain Bifurcated 1 (SETDB1) Expression Predicts Poor Prognosis in Breast Carcinoma

High SET Domain Bifurcated 1 (SETDB1) Expression Predicts Poor Prognosis in Breast Carcinoma

Methyltransferase Setdb1 Promotes Osteoblast Proliferation by Epigenetically Silencing Macrod2 with the Assistance of Atf7ip

A novel association of campomelic dysplasia and hydrocephalus with an unbalanced chromosomal translocation upstream of SOX9

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