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Disrupting DNA Loops Could Be Potential Strategy to Reduce Tumor Proliferation

저자:   업로드:2017-09-15  조회수:

    Baylor College of Medicine researchers report that they discover the mechanism by which normal brain cells regulate the expression of the NFIA, or nuclear factor IA, gene, which is important for both normal brain development and brain tumor growth. The team, which believes its discovery will eventually help improve treatments for brain tumors, published its study (“Glia-Specific Enhancers and Chromatin Structure Regulate NFIA Expression and Glioma Tumorigenesis”) in Nature Neuroscience.

    “By examining the regulation of the transcription factor NFIA in the developing spinal cord, we identified long-range enhancers that recapitulate NFIA expression across glial and neuronal lineages in vivo. Complementary genetic studies found that Sox9–Brn2 and Isl1–Lhx3 regulate enhancer activity and NFIA expression in glial and neuronal populations,” write the investigators. "Chromatin conformation analysis revealed that these enhancers and transcription factors form distinct architectures within these lineages in the spinal cord. In glioma models, the glia-specific architecture is present in tumors, and these enhancers are required for NFIA expression and contribute to glioma formation."

    “By delineating three-dimensional mechanisms of gene expression regulation, our studies identify lineage-specific chromatin architectures and associated enhancers that regulate cell fate and tumorigenesis in the CNS.”

    "We began this project by studying how three components that regulate the expression of the NFIA gene interact with each other in the developing spinal cord in animal models," explains corresponding author Benjamin Deneen, Ph.D., associate professor of neuroscience at the Center for Stem Cell and Regenerative Medicine and member of the Dan L Duncan Comprehensive Cancer Center at Baylor College of Medicine.

    The scientists focused on glial cells, which represent 70% of the cells in the CNS and support the functions of the neurons.

    Dr. Deneen and his colleagues looked at how three levels of gene regulation coordinated their activities to regulate NFIA gene expression. They studied enhancers, transcription factors, and the three-dimensional architecture of the associated DNA.

    The team identified enhancers involved in the regulation of NFIA gene expression using a nontraditional approach. They did not rely on bioinformatics to infer which sections of DNA probably have enhancer activity. Instead, they used living chick embryos to identify enhancer elements in the spinal cord associated with the NFIA gene expression.

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