Related Experiment Video
Updated: Jun 25, 2026
08:54
In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
Functional autonomy of distant-acting human enhancers
Axel Visel1, Jennifer A Akiyama, Malak Shoukry
1Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, CA 94720 USA.
Genomics
|March 10, 2009
Summary
Human developmental enhancers are modular and autonomous, functioning independently even when combined. This suggests enhancer shuffling may have driven the evolution of complex gene expression patterns in vertebrates.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Transcriptional enhancers regulate gene expression in time and space.
- Invertebrate studies suggest enhancers are discrete units, but vertebrate enhancer properties are unclear.
Purpose of the Study:
- To explore the modularity and regulatory autonomy of human developmental enhancers.
- To investigate in vivo combinatorial properties of enhancers in vertebrates.
Main Methods:
- Experimentally concatenated up to four human enhancers from different genes.
- Utilized a transgenic mouse assay to compare compound enhancer activity with single modules.
Main Results:
- Reporter gene activity patterns were additive in all six tested combinations.
- No interference or cross-inhibition observed between closely-positioned heterologous enhancers.
- Regulatory specificity was maintained, even in adjacent anatomical regions like the developing limb bud.
Conclusions:
- Human developmental enhancers are highly modular and functionally autonomous.
- Genomic enhancer shuffling may have contributed to the evolution of complex vertebrate gene expression patterns.
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...
01:25Adrenergic Agonists: Indirect-Acting Agents
Indirect-acting adrenergic agonists potentiate the effects of endogenous catecholamines through different mechanisms without directly binding to adrenoceptors.
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
One mechanism involves depleting stored catecholamines by displacing them from synaptic vesicles. These agents, known as "displacers," are transported into vesicles at the expense of noradrenaline. Examples include amphetamine and tyramine, which lack a catechol moiety, resulting in prolonged action, improved oral bioavailability, and...
01:13Nonconscious Mimicry
Nonconscious mimicry occurs when individuals alter their mannerisms to match the behaviors and expressions of those nearby, without intention.
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...
01:30Spare Receptors
Some receptors remain unoccupied even when an agonist produces a maximal response. Such empty ones are called spare receptors. In presence of spare receptors the maximum effect of an agonist drug is achieved with fewer than 100% of the receptors being occupied. To determine the presence of spare receptors, scientists often compare the concentration of the drug needed to produce 50% of the maximum effect (EC50) with the concentration of the drug needed to occupy 50% of the receptors (Kd). If the...
02:33Combinatorial Gene Control
Combinatorial gene control is the synergistic action of several transcriptional factors to regulate the expression of a single gene. The absence of one or more of these factors may lead to a significant difference in the level of gene expression or repression.
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...
The expression of more than 30,000 genes is controlled by approximately 2000-3000 transcription factors. This is possible because a single transcription factor can recognize more than one regulatory sequence. The specificity in gene...