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Cooperative Binding of Transcription Regulators02:13

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Transcriptional regulators bind to specific cis-regulatory sequences in the DNA to regulate gene transcription. These cis-regulatory sequences are very short, usually less than ten nucleotide pairs in length. The short length means that there is a high probability of the exact same sequence randomly occurring throughout the genome.  Since regulators can also bind to groups of similar sequences, this further increases the chances of random binding. Transcriptional regulators form...
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Cis-regulatory sequences are short fragments of non-coding DNA that are present on the same chromosomes as the genes that they regulate. These fragments serve as binding sites for transcriptional regulators, proteins that are responsible for controlling gene transcription and differential gene expression across cell types in eukaryotes. Cis-regulatory sequences can be close to the gene of interest or thousands of bases away in the DNA sequence; however, those sequences that are further away are...
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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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Deep Learning of Sequence Patterns for CCCTC-Binding Factor-Mediated Chromatin Loop Formation.

Shuzhen Kuang1,2, Liangjiang Wang1

  • 1Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina, USA.

Journal of Computational Biology : a Journal of Computational Molecular Cell Biology
|November 24, 2020
PubMed
Summary
This summary is machine-generated.

A new deep learning model, DeepCTCFLoop, identifies DNA sequence patterns that drive chromatin loop formation. This advances understanding of 3D genome organization and disease-associated variants.

Keywords:
3D genomeCTCFchromatin loopsdeep learningsequence motifs

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CRISPR-Mediated Reorganization of Chromatin Loop Structure
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Area of Science:

  • Genomics
  • Molecular Biology
  • Bioinformatics

Background:

  • The three-dimensional (3D) genome organization is vital for gene regulation.
  • CCCTC-binding factor (CTCF) is key in chromatin interactions, but sequence patterns for loop formation remain unclear.

Purpose of the Study:

  • To discover sequence patterns beyond CTCF motifs that dictate chromatin loop formation.
  • To develop a predictive model for CTCF-mediated chromatin loop formation.

Main Methods:

  • Developed DeepCTCFLoop, a deep learning model, to predict chromatin loop formation using DNA sequences of CTCF motifs and flanking regions.
  • Compared DeepCTCFLoop's performance against CTCF-MP, a machine learning model.

Main Results:

  • DeepCTCFLoop accurately distinguishes CTCF motif pairs that form chromatin loops.
  • DeepCTCFLoop significantly outperforms CTCF-MP using DNA sequences alone.
  • Identified potential roles of transcription factor binding motifs (ZNF384, ZNF263, ASCL1, SP1, ZEB1) in loop formation.
  • Applied DeepCTCFLoop to identify disease-associated variants potentially disrupting chromatin loops.

Conclusions:

  • DeepCTCFLoop provides insights into the complex sequence patterns governing 3D genome organization.
  • The model aids in annotating and prioritizing noncoding variants linked to human diseases.