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Related Concept Videos

Histone Modification02:32

Histone Modification

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The histone proteins have a flexible N-terminal tail extending out from the nucleosome. These histone tails are often subjected to post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitination. Particular combinations of these modifications form “histone codes” that influence the chromatin folding and tissue-specific gene expression.
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The enzyme histone acetyltransferase adds acetyl group to the histones. Another enzyme, histone...
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Histone Variants at the Centromere02:30

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Histone variants are the histone proteins with structural and sequence variations. These variants may be regarded as “mutant” forms that replace their canonical histone counterparts in the nucleosomes. Specific post-translational modifications on the histone variants enable further chromatin complexity and regulate tissue-specific gene expression. The most common histone variants are from histone H2A, H2B, and linker histone H1 families. However, several variants of histone H3...
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Genetic screens are tools used to identify genes and mutations responsible for phenotypes of interest. Genetic screens help identify individuals or a group of people at risk of developing  genetic diseases and help them with early intervention, targeted therapy, and reproductive options.
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Chromosome Replication02:31

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Before a cell can divide, it must accurately replicate all of its chromosomes, including the DNA and its associated histone and non-histone proteins.  This process begins at numerous origins of replication during the S phase of the cell cycle in each of a cell’s chromosomes simultaneously. Certain nucleotides can act as origins of replication, but these sequences are not well defined - especially in complex, multi-cellular, eukaryotic species. The length of DNA that spans an origin...
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Nucleosome Remodeling02:54

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Nucleosomes are the basic units of chromatin compaction. Each nucleosome consists of the DNA bound tightly around a histone core, which makes the DNA inaccessible to DNA binding proteins such as DNA polymerase and RNA polymerase. Hence, the fundamental problem is to ensure access to DNA when appropriate, despite the compact and protective chromatin structure.
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Analysis of Histone Antibody Specificity with Peptide Microarrays
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Screening for histone codebreakers.

Mark T Bedford1

  • 1From the Department of Epigenetics and Molecular Carcinogenesis, The University of Texas MD Anderson Cancer Center, Smithville, Texas 78957 mtbedford@mdanderson.org.

The Journal of Biological Chemistry
|September 2, 2018
PubMed
Summary
This summary is machine-generated.

Researchers developed a high-throughput screening (HTS) assay to discover small molecule inhibitors for the NSD2 enzyme, a key target in various cancers due to its role in histone methylation.

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Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
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Purification of H3 and H4 Histone Proteins and the Quantification of Acetylated Histone Marks in Cells and Brain Tissue
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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Cancer Research

Background:

  • The enzyme NSD2, a lysine methyltransferase, is implicated in cancer development through overexpression and gain-of-function mutations.
  • NSD2 deposits the H3K36me2 mark on histones, a process critical for gene regulation.
  • Targeting NSD2 presents a promising strategy for cancer therapy, but specific inhibitors are lacking.

Purpose of the Study:

  • To establish a robust high-throughput screening (HTS) platform for identifying small molecule inhibitors of NSD2.
  • To facilitate the discovery of novel therapeutic agents targeting NSD2 in cancer.

Main Methods:

  • Development and validation of a HTS assay for NSD2 activity.
  • Screening of chemical libraries to identify potential NSD2 inhibitors.

Main Results:

  • A reliable HTS platform for NSD2 inhibitor discovery was successfully established.
  • The platform enables efficient screening of large compound libraries.

Conclusions:

  • The developed HTS platform is a crucial tool for advancing the discovery of NSD2-targeted cancer therapies.
  • This work lays the foundation for developing novel drugs to treat cancers associated with NSD2 dysregulation.