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Cohesins02:20

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Cohesin protein complexes are a molecular glue that holds two sister chromatids together. They play an important role both in mitosis and meiosis. In mitosis, all cohesin complexes present on the chromosomes are removed before the start of the anaphase stage.
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Meiosis involves two distinct rounds of chromosomal segregation and cell divisions— Meiosis I followed by Meiosis II – producing four daughter cells. Meiosis I includes the separation of...
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At the transition from prophase to metaphase, there is a reduction in cohesion along the chromosomal arms, resulting in the resolution of sister chromatids. However, residual cohesin connections remain to hold the sister chromatids together until the transition from metaphase to anaphase. The residual connection prevents any premature separation of sister chromatids, blocking the risks of aneuploidy within the daughter cells.
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The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
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Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
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DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart,...
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CRISPR-Mediated Reorganization of Chromatin Loop Structure
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Cohesin Loss Eliminates All Loop Domains.

Suhas S P Rao1, Su-Chen Huang2, Brian Glenn St Hilaire3

  • 1The Center for Genome Architecture, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA; Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA.

Cell
|October 7, 2017
PubMed
Summary

Degrading cohesin eliminates loop domains but not compartment domains in the human genome. Cohesin loss affects active genes by causing superenhancers to co-localize, impacting gene regulation.

Keywords:
4D NucleomeCTCFHi-Cchromatin loopscohesiongene regulationgenome architectureloop extrusionnuclear compartmentssuperenhancers

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Area of Science:

  • Genomics
  • Molecular Biology
  • Epigenetics

Background:

  • The human genome is organized into hierarchical structures, including loop domains and compartment domains.
  • Loop domains are formed by CTCF and cohesin binding, while compartment domains arise from co-segregation of genomic intervals with similar histone marks.

Purpose of the Study:

  • To investigate the role of cohesin in genome organization and gene regulation.
  • To determine the effects of cohesin degradation on loop domains, compartment domains, and gene expression.

Main Methods:

  • Cohesin degradation was induced in human cells.
  • Genome-wide contact frequencies were analyzed using techniques like Hi-C.
  • Gene expression and histone marks were assessed.

Main Results:

  • Elimination of cohesin led to the complete loss of loop domains.
  • Compartment domains and histone marks remained unaffected by cohesin loss.
  • Cohesin depletion caused superenhancers to co-localize, affecting the regulation of nearby genes.
  • Restoration of cohesin resulted in rapid re-formation of loop domains, with many megabase-sized loops recovering in under an hour.

Conclusions:

  • Cohesin is essential for the formation and maintenance of loop domains.
  • Loop domain formation is distinct from compartment domain formation.
  • Cohesin plays a crucial role in regulating gene expression through superenhancer organization and loop extrusion.