Related Experiment Video
Updated: Aug 11, 2026
11:36
An Integrated Workflow to Study the Promoter-Centric Spatio-Temporal Genome Architecture in Scarce Cell Populations
Published on: April 21, 2023
Long-range upstream and downstream enhancers control distinct subsets of the complex spatiotemporal Sox9 expression
Stefan Bagheri-Fam1, Francisco Barrionuevo, Ulrike Dohrmann
1Institute of Human Genetics and Anthropology, University of Freiburg, Breisacherstr. 33, D-79106 Freiburg, Germany.
Developmental Biology
|February 7, 2006
Summary
SOX9 is crucial for development. Researchers identified conserved regulatory elements (enhancers) that control SOX9 gene expression in specific tissues like the neural crest and inner ear.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- SOX9 is an evolutionarily conserved transcription factor vital for multiple tissue developments.
- Previous studies identified conserved non-coding elements near the SOX9 gene.
Purpose of the Study:
- To investigate the regulatory potential of conserved elements (E1-E7) located near the SOX9 gene.
- To understand the tissue-specific expression patterns controlled by these elements and the SOX9 promoter.
Main Methods:
- Assayed regulatory potential of elements E1-E7 using lacZ reporter gene in transgenic mice.
- Utilized a minimal mouse Sox9 promoter (529 bp).
- Investigated beta-catenin dependency for E3-directed expression in neural crest cells.
Main Results:
- Three elements (E1, E3, E7) and the Sox9 promoter control distinct tissue-specific expression patterns.
- E3 directs expression to cranial neural crest and inner ear.
- E1 controls expression in node, notochord, gut, bronchial epithelium, and pancreas.
- E7 and the promoter regulate neuroectodermal expression (telencephalon, midbrain, spinal cord, hindbrain).
- E3-driven neural crest expression is beta-catenin dependent.
- Identified conserved transcription factor binding sites in E3.
- E1 is a cis-regulatory element conserved across vertebrates and invertebrates.
Conclusions:
- SOX9 expression is regulated by multiple conserved cis-regulatory elements.
- E3 and E1 play significant roles in neural crest, inner ear, and other developmental processes.
- Regulatory mechanisms for SOX9 in cranial neural crest involve beta-catenin.
- Some cis-regulatory sequences controlling developmental genes are ancient and conserved across phyla.
Related Concept Videos
02:36RNA Polymerase II Accessory Proteins
Proteins that regulate transcription can do so either via direct contact with RNA Polymerase or through indirect interactions facilitated by adaptors, mediators, histone-modifying proteins, and nucleosome remodelers. Direct interactions to activate transcription is seen in bacteria as well as in some eukaryotic genes. In these cases, upstream activation sequences are adjacent to the promoters, and the activator proteins interact directly with the transcriptional machinery. For example, in...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
02:23Master Transcription Regulators
Master transcription regulators are regulatory proteins that are predominantly responsible for regulating the expression of multiple genes. Often these genes work in concert to drive a complex process. Activation of a master transcription regulator can lead to a cascade of transcriptional activation necessary for that outcome. These regulators can directly bind to the regulatory sequences of the various genes involved, or they can indirectly regulate transcription by binding to regulatory...
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...
02:35Chromatin Position Affects Gene Expression
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.
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
Topologically Associated Domains (TADs)
The 3-dimensional positioning of chromatin in the nucleus influences the timing and level of...
02:40The Eukaryotic Promoter Region
The eukaryotic promoter region is a segment of DNA located upstream of a gene. It contains an RNA polymerase binding site, a transcription start site, and several cis-regulatory sequences. The proximal promoter region is located in the vicinity of the gene and has cis-regulatory sequences and the core promoter. The core promoter is the binding site for RNA polymerase and is usually located between -35 and +35 nucleotides from the transcription start site. The distal promoter regions are...