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Related Concept Videos

Cooperative Binding of Transcription Regulators02:13

Cooperative Binding of Transcription Regulators

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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 Sequences02:02

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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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Regulation of Hematopoietic Stem Cells01:01

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All blood and immune cells are produced from the multipotent hematopoietic stem cells (HSCs) by the process of hematopoiesis. However, they all have a limited life span. In addition, many are depleted in immune surveillance or combatting an injury or infection. This makes blood one of the most regenerative tissues. Hematopoiesis helps replenish these blood and immune cells, restoring the body's normal functioning. However, overproduction of blood and immune cells can make them cancerous or...
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Gene transcription is regulated by the synergistic action of several proteins that form a complex at a gene regulatory site. This is observed in eukaryotes, where the regulation of gene expression is a complex process. Regulatory proteins in eukaryotes can broadly be classified into two types – regulators that bind directly to specific DNA sequences and co-regulators that associate with regulatory proteins but cannot directly bind to the DNA. These co-regulators are further divided into...
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Dynamic CTCF binding directly mediates interactions among cis-regulatory elements essential for hematopoiesis.

Qian Qi1, Li Cheng1, Xing Tang1

  • 1Department of Hematology, St. Jude Children's Research Hospital, Memphis, TN.

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CCCTC-binding factor (CTCF) dynamically regulates gene expression in blood cell development. This study reveals CTCF

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Direct Induction of Hemogenic Endothelium and Blood by Overexpression of Transcription Factors in Human Pluripotent Stem Cells
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Area of Science:

  • Genomics
  • Epigenetics
  • Molecular Biology

Background:

  • Constitutive CCCTC-binding factor (CTCF) sites maintain chromatin structures.
  • The role of CTCF in cell-type-specific transcription is not well understood.

Purpose of the Study:

  • To investigate the function of CTCF in gene regulation during blood cell development.
  • To identify dynamic, cell-type-specific CTCF binding sites.

Main Methods:

  • Examined CTCF occupancy in primary blood cells.
  • Utilized CRISPR-Cas9 for perturbation experiments.
  • Analyzed CTCF-binding motifs and enhancer-promoter interactions.

Main Results:

  • Identified dynamic, cell-type-specific CTCF binding sites colocalizing with lineage-specific transcription factors.
  • Found these sites enriched for SNPs associated with blood cell traits.
  • Demonstrated CTCF's critical role in red blood cell development and erythropoiesis via perturbation experiments.
  • Showed deletion of CTCF motifs abolished enhancer-promoter interactions for erythroid genes like RBM38, causing abnormal erythropoiesis.

Conclusions:

  • CTCF has a novel, cell-type-specific function in facilitating interactions between distal regulatory elements and target promoters.
  • Dynamic CTCF binding is crucial for transcriptional regulation during hematopoiesis.