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Related Concept Videos

Non-Canonical Wnt Signaling Pathways01:41

Non-Canonical Wnt Signaling Pathways

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Wnt is a zygotic effect gene that is expressed during very early embryonic development. It regulates various processes in animals starting from early development through the adult stage, such as organogenesis in the embryo and maintenance of neuronal and blood stem cells. Wnt proteins can induce a wide variety of intracellular pathways depending upon the specific abilities of different Wnt ligands to form a complex with shared and cognate receptors in the presence of different co-receptors. The...
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The gene encoding the main signaling molecules of the Wnt signaling pathways (the Wnt proteins) was discovered almost four decades ago by Nüsslein-Volhard and Wieschaus. They identified and originally named the gene "wingless" (wg) after a phenotype discovered during their landmark genetic screen in Drosophila for body pattern defects. At around the same time, another researcher named Harold Varmus found that a murine tumor virus activates the mammalian wg homolog, Int-1, which...
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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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Chromatin Modification in iPS Cells01:32

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Chromatin modification alters gene expression; therefore, scientists can add histone-modifying enzymes, histone variants, and chromatin remodeling complexes to somatic cells to aid reprogramming into pluripotent stem (iPS) cells.
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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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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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Related Experiment Video

Updated: Sep 7, 2025

High-Resolution Mapping of Protein-DNA Interactions in Mouse Stem Cell-Derived Neurons using Chromatin Immunoprecipitation-Exonuclease ChIP-Exo
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Chromatin interaction maps identify Wnt responsive cis-regulatory elements coordinating Paupar-Pax6 expression in

Ioanna Pavlaki1, Michael Shapiro1,2, Giuseppina Pisignano1

  • 1Department of Biology and Biochemistry, University of Bath, Bath, United Kingdom.

Plos Genetics
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Researchers uncovered how adjacent brain genes, long non-coding RNA (lncRNA) and mRNA, are co-expressed. The TCF7L2 protein coordinates this process, revealing new insights into neuronal development and gene regulation.

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Chromatin Interaction Analysis with Paired-End Tag Sequencing ChIA-PET for Mapping Chromatin Interactions and Understanding Transcription Regulation
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Chromatin Interaction Analysis with Paired-End Tag Sequencing ChIA-PET for Mapping Chromatin Interactions and Understanding Transcription Regulation

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Long non-coding RNAs (lncRNAs) in the central nervous system are often located near protein-coding genes involved in transcriptional control.
  • Co-expression of neighboring lncRNA-protein coding gene pairs is common in the nervous system, suggesting coordinated roles in neuronal development and function.
  • The precise regulatory mechanisms governing the co-expression of these adjacent genes remain largely unknown.

Purpose of the Study:

  • To investigate the cis-regulatory interaction landscape of the neuro-developmental Paupar-Pax6 lncRNA-mRNA locus using high-resolution NG Capture-C.
  • To understand the chromatin architecture changes and regulatory elements involved in the co-expression of Paupar and Pax6 in neurons.
  • To identify transcription factors that coordinate the co-expression of Paupar and Pax6.

Main Methods:

  • High-resolution NG Capture-C was employed to map cis-regulatory interactions.
  • Analysis of chromatin architecture changes associated with Paupar-Pax6 expression.
  • Identification of transcription factor binding sites and their role in gene co-regulation.

Main Results:

  • Defined the chromatin architecture changes linked to high Paupar-Pax6 expression in neurons.
  • Identified both shared and promoter-selective cis-regulatory interactions governing Paupar-Pax6 co-expression.
  • Discovered that the TCF7L2 transcription factor binds to specific cis-regulatory elements, coordinating Paupar and Pax6 co-expression.
  • Revealed distinct roles for Paupar in Pax6 expression control, with its DNA locus containing a TCF7L2-bound silencer and the transcript acting as a Pax6 activator.

Conclusions:

  • Provides crucial insights into the chromatin interactions, signaling pathways (Wnt pathway), and transcription factors controlling the co-expression of adjacent lncRNAs and protein-coding genes in the brain.
  • Highlights the role of TCF7L2 in orchestrating the coordinated expression of lncRNA-mRNA pairs.
  • Elucidates the dual function of the Paupar transcript and its locus in regulating Pax6 expression.