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Related Concept Videos

Epigenetic Regulation01:37

Epigenetic Regulation

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Epigenetic changes alter the physical structure of the DNA without changing the genetic sequence and often regulate whether genes are turned on or off. This regulation ensures that each cell produces only proteins necessary for its function. For example, proteins that promote bone growth are not produced in muscle cells. Epigenetic mechanisms play an essential role in healthy development. Conversely, precisely regulated epigenetic mechanisms are disrupted in diseases like cancer.
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Chromatin is the massive complex of DNA and proteins packaged inside the nucleus. The complexity of chromatin folding and how it is packaged inside the nucleus greatly influences  access to genetic information. Generally, the nucleus' periphery is considered transcriptionally repressive, while the cell's interior is considered a transcriptionally active area. 
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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Targeted DNA Methylation Analysis by Next-generation Sequencing
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CpG methylation patterns are associated with gene expression variation in osteosarcoma.

Qiang Wang1

  • 1Department of Orthopedics, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.

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|June 1, 2017
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Summary

This study reveals key methylation changes linked to gene expression in osteosarcoma, identifying potential drivers like SEZ6L2 that promote cancer cell proliferation and metastasis.

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Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Osteosarcoma is a prevalent childhood cancer with a poor prognosis.
  • The molecular mechanisms driving osteosarcoma pathogenesis are not fully understood.
  • Understanding gene expression and methylation alterations is crucial for elucidating osteosarcoma development.

Purpose of the Study:

  • To investigate the association between DNA methylation and gene expression changes in osteosarcoma cell lines.
  • To identify differentially expressed genes (DEGs) and differentially methylated sites in osteosarcoma.
  • To construct a transcriptional regulatory network integrating methylation and gene expression data.

Main Methods:

  • Utilized microarray data from the Gene Expression Omnibus (GSE36004) for genome-wide methylation and gene expression analysis.
  • Identified DEGs using the genefilter package and differentially methylated sites using the CpGassoc package in R.
  • Constructed a transcriptional regulatory network and performed functional annotation using the DAVID online tool.

Main Results:

  • Identified 75 methylated sites within transcription factor binding regions, potentially regulating 75 DEGs via 83 transcription factors.
  • Discovered that seizure related 6 homolog like 2 (SEZ6L2), kin of IRRE like (KIRREL), centrosomal protein 72 (CEP72), and cyclin-dependent kinase 4 (CDK4) were significantly regulated.
  • Functional annotation indicated that upregulated genes are predominantly involved in cell cycle pathways, suggesting a role in proliferation and metastasis.

Conclusions:

  • Specific methylation sites are associated with the upregulation of SEZ6L2, KIRREL, CEP72, and CDK4 in osteosarcoma.
  • These molecular alterations may play a significant role in osteosarcoma pathogenesis by promoting cell proliferation and metastasis.
  • The findings provide insights into the epigenetic regulation of osteosarcoma and potential therapeutic targets.