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Related Concept Videos

Chromatin Position Affects Gene Expression02:35

Chromatin Position Affects Gene Expression

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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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Euchromatin01:01

Euchromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions take up more dye, appearing darker, while the less-compact areas take up less dye and appear lighter. Based on the compaction level, chromatins are classified into two primary forms – euchromatin and heterochromatin.
Euchromatin is the less dense region of the chromatin and stains lighter. Euchromatin contains histone H3 extensively...
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Heterochromatin02:38

Heterochromatin

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The extent of chromatin compaction can be studied by staining chromatin using specific DNA binding dyes. Under the microscope, the dense-compacted regions that take up more dye are called heterochromatin. Heterochromatin is further classified into two forms – constitutive heterochromatin and facultative heterochromatin.
Constitutive heterochromatin: It is a highly compact region of chromatin that is mostly concentrated in the centromere and telomere. Unlike euchromatin, the amino acid at...
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Spreading of Chromatin Modifications02:25

Spreading of Chromatin Modifications

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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
The writer...
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Nucleosome Remodeling02:54

Nucleosome Remodeling

9.3K
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.
Nucleosome remodeling complex
Eukaryotic cells have specialized enzymes called ATP-dependent nucleosome remodeling enzymes. These enzymes...
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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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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
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Moonlighting chromatin: when DNA escapes nuclear control.

Jeeshan Singh1,2, Michael Boettcher3, Maximilian Dölling4

  • 1Department of Internal Medicine 3, Rheumatology and Immunology, Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) and Universitätsklinikum Erlangen, Erlangen, Germany.

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Summary

Extracellular chromatin, released as neutrophil extracellular traps (NETs), drives many diseases. Dysregulated NET formation and impaired clearance contribute to inflammatory and occlusive disorders, necessitating targeted therapies.

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Area of Science:

  • Immunology
  • Pathology
  • Cell Biology

Background:

  • Extracellular chromatin, particularly neutrophil extracellular traps (NETs), plays a critical role in disease pathogenesis.
  • DNA within NETs interacts with the interferon system, acts as an autoantigen, and scaffolds innate immune proteins.
  • Insufficient clearance of extruded chromatin contributes to immune-inflammatory and occlusive disorders.

Purpose of the Study:

  • To discuss the cellular events of extracellular chromatin and NET formation.
  • To examine the consequences of dysregulated NET formation.
  • To explore the imbalance between NET formation and clearance in various diseases.

Main Methods:

  • Review of cellular events in chromatin extrusion and NETosis.
  • Analysis of the role of NETs in pathological conditions.
  • Discussion of therapeutic strategies targeting NET formation and clearance.

Main Results:

  • Extracellular chromatin release and NET formation are key pathological processes.
  • Dysregulated NET formation contributes to vascular occlusion, lung disease, autoimmune disorders, cancer, adhesions, and spinal cord injury.
  • An imbalance between NET formation and clearance exacerbates disease progression.

Conclusions:

  • Targeting chromatin decondensation pathways during NET formation is crucial for therapy.
  • Enhancing the clearance of extracellular chromatin presents a viable therapeutic approach.
  • Understanding NET dynamics is essential for developing effective treatments for a wide range of diseases.