Related Experiment Video
Updated: Jul 15, 2026
08:12
A Web-Based Workflow for Selecting Gene- and Tissue-Specific Enhancers
Published on: July 18, 2025
Human GLI3 intragenic conserved non-coding sequences are tissue-specific enhancers
Amir Ali Abbasi1, Zissis Paparidis, Sajid Malik
1Institute of Human Genetics, Philipps-University, Marburg, Germany.
Plos One
|April 12, 2007
Summary
Researchers identified ancient DNA sequences within human GLI3 introns that regulate gene expression. These conserved non-coding elements (CNEs) are crucial for controlling development and evolution of gene regulation.
Area of Science:
- Developmental Biology
- Evolutionary Genetics
- Molecular Biology
Background:
- The zinc-finger transcription factor GLI3 is vital for development, mediating Sonic hedgehog (SHH) signaling.
- Precise temporal and spatial control of GLI3 expression is essential for proper development.
- Regulatory cis-acting elements controlling GLI3 expression remained largely uncharacterized.
Purpose of the Study:
- To identify and characterize cis-acting DNA elements regulating human GLI3 gene expression.
- To investigate the evolutionary conservation and functional significance of these regulatory elements.
Main Methods:
- Bioinformatic analysis to identify conserved non-coding elements (CNEs) in human GLI3 introns.
- Functional assays involving transient transfection of CNEs in human cell lines.
- Reporter gene assays in zebrafish embryos to assess tissue-specific enhancer activity.
- Deletion construct analysis to pinpoint essential regulatory sequences.
Main Results:
- Identified 11 ancient DNA signatures conserved from fish to humans within GLI3 introns, located in larger tetrapod-specific CNEs.
- Demonstrated that full-length CNEs function as cell-type-specific enhancers of gene transcription.
- Showed conserved enhancer activity in zebrafish, directing tissue-specific reporter gene expression.
- Deletion assays revealed that human-fish conserved sequences are essential but not sufficient for full enhancer activity.
Conclusions:
- GLI3 intronic CNEs contain ancient regulatory sequences crucial for development.
- Enhancer activity results from a combination of ancient core sequences and more recently evolved flanking sequences.
- This suggests a model for the evolution of cis-regulatory elements through the stepwise addition of regulatory potential around conserved nuclei.
More Related Videos
Related Concept Videos
02:51Multi-species Conserved Sequences
Next-generation sequencing technologies have created large genomic databases of a variety of animals and plants. Ever since the human genome project was completed, scientists studied the genome of primates, mammals, and other phylogenetically distant living beings. Such large-scale studies have provided new insights into the evolutionary relationship between organisms.
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
Although the genome of each species varies greatly from each other, a few sequences are highly conserved. Such conserved DNA...
01:30General Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:16Transcription Factors
Tissue-specific transcription factors contribute to diverse cellular functions in mammals. For example, the gene for beta globin, a major component of hemoglobin, is present in all cells of the body. However, it is only expressed in red blood cells because the transcription factors that can bind to the promoter sequences of the beta globin gene are only expressed in these cells. Tissue-specific transcription factors also ensure that mutations in these factors may impair only the function of...
02:32Position-effect Variegation
In 1928, a German botanist Emil Heitz observed the moss nuclei with a DNA binding dye. He observed that while some chromatin regions decondense and spread out in the interphase nucleus, others do not. He termed them euchromatin and heterochromatin, respectively. He proposed that the heterochromatin regions reflect a functionally inactive state of the genome. It was later confirmed that heterochromatin is transcriptionally repressed, and euchromatin is transcriptionally active chromatin.
02:02Cis-regulatory Sequences
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...
02:02Cis-regulatory Sequences
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...