scholarly journals Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration

2018 ◽  
Vol 115 (52) ◽  
pp. E12417-E12426 ◽  
Author(s):  
Young Mi Oh ◽  
Marcus Mahar ◽  
Eric E. Ewan ◽  
Kathleen M. Leahy ◽  
Guoyan Zhao ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Axon Regeneration ◽  
Ring Finger ◽  
Suppressor Gene ◽  
Dna Methyltransferases ◽  
Epigenetic Mechanism ◽  
Nerve Lesion ◽  
Axon Injury ◽  
Epigenetic Regulator

Injured peripheral sensory neurons switch to a regenerative state after axon injury, which requires transcriptional and epigenetic changes. However, the roles and mechanisms of gene inactivation after injury are poorly understood. Here, we show that DNA methylation, which generally leads to gene silencing, is required for robust axon regeneration after peripheral nerve lesion. Ubiquitin-like containing PHD ring finger 1 (UHRF1), a critical epigenetic regulator involved in DNA methylation, increases upon axon injury and is required for robust axon regeneration. The increased level of UHRF1 results from a decrease in miR-9. The level of another target of miR-9, the transcriptional regulator RE1 silencing transcription factor (REST), transiently increases after injury and is required for axon regeneration. Mechanistically, UHRF1 interacts with DNA methyltransferases (DNMTs) and H3K9me3 at the promoter region to repress the expression of the tumor suppressor gene phosphatase and tensin homolog (PTEN) and REST. Our study reveals an epigenetic mechanism that silences tumor suppressor genes and restricts REST expression in time after injury to promote axon regeneration.

scholarly journals The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

Genes ◽  
2019 ◽  
Vol 10 (2) ◽  
pp. 172 ◽  
Author(s):  
Hemant Gujar ◽  
Daniel Weisenberger ◽  
Gangning Liang
Keyword(s):  
Dna Methylation ◽  
Cytosine Methylation ◽  
De Novo ◽  
Ring Finger ◽  
Dna Methyltransferases ◽  
Epigenetic Modifications ◽  
Hard Copy ◽  
Physiological Processes ◽  
New Gene ◽  
Cpg Dinucleotide

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.

Abstract A18: Expression of the tumor suppressor gene RARRES1 in the differentiation hierarchy of breast cancer is regulated by DNA methylation

2016 ◽  
Author(s):  
Krysta Mila Coyle ◽  
Dejan Vidovic ◽  
Cheryl A. Dean ◽  
Margaret Lois Thomas ◽  
Mohammad Sultan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene

scholarly journals Expression of the candidate tumor suppressor gene hSRBC is frequently lost in primary lung cancers with and without DNA methylation

Oncogene ◽  
2005 ◽  
Vol 24 (41) ◽  
pp. 6249-6255 ◽  
Author(s):  
Sabine Zöchbauer-Müller ◽  
Kwun M Fong ◽  
Joseph Geradts ◽  
Xie Xu ◽  
Sonja Seidl ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Suppressor Gene ◽  
Lung Cancers ◽  
Candidate Tumor Suppressor ◽  
Candidate Tumor Suppressor Gene

scholarly journals Histone modifications and silencing prior to DNA methylation of a tumor suppressor gene

Cancer Cell ◽  
2003 ◽  
Vol 3 (1) ◽  
pp. 89-95 ◽  
Author(s):  
Kurtis E Bachman ◽  
Ben Ho Park ◽  
Ina Rhee ◽  
Harith Rajagopalan ◽  
James G Herman ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Histone Modifications ◽  
Suppressor Gene

scholarly journals Evolutionary History of DNA Methylation Related Genes in Bivalvia: New Insights From Mytilus galloprovincialis

2021 ◽  
Vol 9 ◽  
Author(s):  
Marco Gerdol ◽  
Claudia La Vecchia ◽  
Maria Strazzullo ◽  
Pasquale De Luca ◽  
Stefania Gorbi ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Mytilus Galloprovincialis ◽  
Adult Life ◽  
Dna Methyltransferases ◽  
Methylation Pattern ◽  
Epigenetic Mechanism ◽  
Specific Gene ◽  
Fundamental Information ◽  
Genome Activity

DNA methylation is an essential epigenetic mechanism influencing gene expression in all organisms. In metazoans, the pattern of DNA methylation changes during embryogenesis and adult life. Consequently, differentiated cells develop a stable and unique DNA methylation pattern that finely regulates mRNA transcription during development and determines tissue-specific gene expression. Currently, DNA methylation remains poorly investigated in mollusks and completely unexplored in Mytilus galloprovincialis. To shed light on this process in this ecologically and economically important bivalve, we screened its genome, detecting sequences homologous to DNA methyltransferases (DNMTs), methyl-CpG-binding domain (MBD) proteins and Ten-eleven translocation methylcytosine dioxygenase (TET) previously described in other organisms. We characterized the gene architecture and protein domains of the mussel sequences and studied their phylogenetic relationships with the ortholog sequences from other bivalve species. We then comparatively investigated their expression levels across different adult tissues in mussel and other bivalves, using previously published transcriptome datasets. This study provides the first insights on DNA methylation regulators in M. galloprovincialis, which may provide fundamental information to better understand the complex role played by this mechanism in regulating genome activity in bivalves.

scholarly journals DNA Hypermethylation Modification Promotes the Development of Hepatocellular Carcinoma by Depressing the Tumor Suppressor Gene ZNF334

2021 ◽  
Author(s):  
Da-peng Sun ◽  
Xiao-jie Gan ◽  
Lei Liu ◽  
Yuan Yang ◽  
Dong-yang Ding ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Dna Methylation ◽  
Tumor Suppressor ◽  
Liver Cancer ◽  
Tumor Suppressor Gene ◽  
Clinical Evidence ◽  
Early Stage ◽  
Suppressor Gene ◽  
Dna Hypermethylation ◽  
Dysplastic Nodules

Abstract Background: DNA methylation plays a pivotal role in the development and progression of tumors, but studies focused on the dynamic changes of DNA methylation in the development of hepatocellular carcinoma (HCC) are rare. This manuscript is aimed to construct pre- and early DNA methylation maps of liver cancer of the same genetic background, as well as to reveal the mechanism of epigenetics regulating gene expression during the development of liver cancer, thus providing new targets and clinical evidence for early diagnosis and shedding lights on the precise treatment for liver cancer. Methods: The study includes 5 patients who were chronic hepatitis B virus infected, clinically diagnosed as primary liver cancer and pathologically diagnosed as early liver cancer with liver dysplastic nodules. Liver fibrosis tissues, dysplastic nodules and early HCC tissues from these patients have been used to measure DNA methylation. Results: We report significant differences in the DNA methylation spectrum of three types of tissues. In the early stage of HCC, DNA hypermethylation of tumor suppressor genes is predominant. Additionally, DNA hypermethylation in the early stage of HCC changes the binding of transcription factor P53 to the promoter of tumor suppressor gene ZNF334, and inhibits the expression of ZNF334 at the transcription level. Furthermore, through a series of in vivo and in vitro experiments, we have clarified the exacerbation effect of tumor suppressor gene ZNF334 deletion in the occurrence of HCC. Combined with clinical data, we found that the overall survival and disease-free survival of patients with high ZNF334 expression are longer than the lower one. Conclusions: We constructed a sequential map of DNA methylation modification during the occurrence of HCC, and clarified the biological function and regulatory mechanism of the tumor suppressor gene ZNF334, which is regulated by related DNA methylation sites, and also provide new targets and clinical evidence for the early diagnosis and precise treatment of liver cancer.

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