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Related Concept Videos

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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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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The histone proteins in the nucleosomes are post-translationally modified (PTM) to increase or decrease access to DNA. The commonly observed PTMs are methylation, acetylation, phosphorylation, and ubiquitination of lysine amino acids in the histone H3 tail region. These histone modifications have specific meaning for the cell. Hence, they are called "histone code". The protein complex involved in histone modification is termed as "reader-writer" complex.
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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 process of chromosome duplication during cell division requires genome-wide disruption and re-assembly of chromatin. The chromatin structure must be accurately inherited, reassembled, and maintained in the daughter cells to ensure lineage propagation.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Identifying genetic variants associated with chromatin looping and genome function.

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We identified novel genetic variants influencing chromatin looping in T cells by analyzing HiChIP data. These variants, called interaction QTLs (iQTLs), link genotype to gene expression and cell connectivity.

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Area of Science:

  • Genomics
  • Immunology
  • Epigenetics

Background:

  • Understanding genetic regulation of gene expression is crucial in immunology.
  • Chromatin conformation plays a key role in regulating gene activity.
  • Previous studies focused on eQTLs and histone QTLs, but the role of chromatin contacts in genetic variation is less explored.

Purpose of the Study:

  • To identify genetic variants associated with chromatin contact variations in naïve CD4 T cells.
  • To explore the relationship between chromatin contact QTLs (iQTLs) and gene expression QTLs (eQTLs).
  • To define novel QTLs, including connectivity-QTLs, and their impact on cell-specific gene expression.

Main Methods:

  • Generated a comprehensive HiChIP dataset from 30 donors of naïve CD4 T cells (nCD4).
  • Performed QTL mapping to identify iQTLs associated with genotype-dependent variation in HiChIP contacts.
  • Integrated iQTL data with existing eQTL and histone QTL datasets, and GWAS variants.

Main Results:

  • Identified numerous iQTLs in nCD4 cells, showing substantial overlap with known eQTLs and histone QTLs.
  • Discovered a subset of nCD4 iQTLs that predict gene expression trends in memory CD4 T cell subsets.
  • Defined connectivity-QTLs, linking genotype-dependent chromatin contact changes across broad genomic regions.

Conclusions:

  • Chromatin contacts provide a complementary modality for QTL mapping.
  • HiChIP-based iQTL analysis is powerful for discovering novel QTLs.
  • This approach links genetic variation to cell-specific gene expression and regulatory network connectivity.