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Related Concept Videos

Chromatin Packaging02:21

Chromatin Packaging

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Each human somatic cell contains 6 billion base-pairs of DNA. Each base-pair is 0.34 nm long, which means that each diploid cell contains a staggering 2 meters of DNA. How is such a long DNA strand packed inside a nucleus measuring only 10 - 20 microns in diameter? 
The chromatin
In combination with specialized DNA binding protein called Histones, the DNA double helix forms a compact DNA: protein complex called chromatin. The chromatin itself is further compacted into higher-order...
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Chromatin Packaging01:32

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Each human somatic cell contains 6 billion base pairs of DNA. Each base pair is 0.34 nm long, meaning each diploid cell contains a staggering 2 meters of DNA. This long DNA strand is packed inside a nucleus measuring only 10-20 microns in diameter with the help of specialized DNA-binding proteins called histones. Together they form a compact DNA-protein complex called chromatin. The chromatin is further compacted into higher-order structures. The highest level of compaction is achieved during...
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Inheritance of Chromatin Structures03:17

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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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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. 
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the...
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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.
Writers
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Deciphering High-Resolution 3D Chromatin Organization via Capture Hi-C
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Characterizing chromatin folding coordinate and landscape with deep learning.

Wen Jun Xie1, Yifeng Qi1, Bin Zhang1

  • 1Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.

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Deep learning identified a chromatin folding pathway in cohesin-depleted cells, revealing how topological domains (TADs) form. While energetically favorable, folding is incomplete due to entropic penalties, impacting TADs.

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Area of Science:

  • Genomics and Molecular Biology
  • Computational Biology and Bioinformatics

Background:

  • Genome organization dictates the spatial environment for gene transcription.
  • High-resolution characterization of genome organization has advanced, but underlying molecular mechanisms remain unclear.
  • Cohesin plays a crucial role in establishing genome architecture, including topologically associating domains (TADs).

Purpose of the Study:

  • To elucidate the molecular mechanisms governing chromatin folding and the establishment of genome organization.
  • To analyze chromatin structure heterogeneity and fluctuations using advanced computational methods.
  • To identify key factors and pathways involved in the formation of topologically associating domains (TADs).

Main Methods:

  • Application of a deep-learning approach, specifically a variational autoencoder (VAE), to analyze single-cell imaging data of chromatin structures.
  • Utilizing statistical mechanical analysis to interpret chromatin folding pathways and energetic landscapes.
  • Investigating cohesin-depleted cellular models to understand the role of cohesin in TAD formation.

Main Results:

  • A reaction coordinate for chromatin folding was identified, connecting heterogeneous structures in cohesin-depleted cells to TAD formation.
  • Folding into wild-type-like structures was found to be energetically favorable, potentially driven by phase separation of active and repressive chromatin.
  • Despite favorable energetics, entropic penalties prevented complete folding, leading to partially folded structures and loss of TADs in averaged contact maps.

Conclusions:

  • Machine learning, combined with statistical mechanics, provides powerful tools for analyzing complex chromatin structural ensembles.
  • Cohesin's role in TAD formation is linked to overcoming entropic penalties to achieve complete chromatin folding.
  • Understanding chromatin folding pathways is essential for deciphering genome organization and its functional implications.