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Related Concept Videos

Inheritance of Chromatin Structures03:17

Inheritance of Chromatin Structures

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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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Epigenetic Regulation01:37

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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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Epigenetic Regulation01:46

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Chromatin Position Affects Gene Expression02:35

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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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Histone Modification02:32

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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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Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
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Mapping Alzheimer's Disease Variants to Their Target Genes Using Computational Analysis of Chromatin Configuration
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Chromatin Looping Links Target Genes with Genetic Risk Loci for Dermatological Traits.

Chenfu Shi1, Helen Ray-Jones2, James Ding1

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Chromatin looping connects disease risk variants to target genes. Our study reveals skin-related factors are crucial in skin disorder risk by analyzing active chromatin interactions.

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Area of Science:

  • Genomics
  • Molecular Biology
  • Dermatology

Background:

  • Chromatin looping between regulatory elements and gene promoters is a key mechanism for how genetic variants influence gene expression.
  • Understanding these interactions is vital for deciphering the genetic basis of complex diseases, particularly skin disorders.

Purpose of the Study:

  • To investigate chromatin interactions in skin cells and T cells to identify gene targets of disease risk variants.
  • To explore the functional relevance of these interactions in the context of skin-related disorders.

Main Methods:

  • Utilized H3K27ac HiChIP to map the active chromatin interactome in keratinocytes and CD8+ T cells.
  • Integrated public datasets from lymphoblastoid cell lines and CD4+ T cells.
  • Performed pathway enrichment analysis on identified interacting genes.

Main Results:

  • Identified gene targets at risk loci for skin-related disorders, including psoriasis, psoriatic arthritis, and melanoma.
  • Discovered enrichment of relevant pathways, such as cytokine response and replicative senescence.
  • Re-assigned a psoriasis-associated variant (rs10794648) from IFNLR1 to GRHL3, a gene critical for skin development and repair.

Conclusions:

  • Chromatin interactions provide insights into the genetic architecture of skin diseases.
  • Skin-related factors play a significant role in the risk of developing skin disorders.
  • The study highlights the importance of considering gene-environment interactions and regulatory element function in disease etiology.