Related Experiment Video
Updated: Jun 4, 2026
08:54
In vivo Application of the REMOTE-control System for the Manipulation of Endogenous Gene Expression
Published on: March 29, 2019
An Activator of Tailless' Repressor Function Stimulates Anti-Neurodegenerative Gene Expression.
Emily C Hank1, Romy Busch1, Úrsula López-García1
1Ludwig-Maximilians-Universität München, Department of Pharmacy, Munich 81377, Germany.
Journal of Medicinal Chemistry
|June 3, 2026
Summary
Researchers developed potent activators for the tailless (TLX) transcription factor. These activators showed promise for neurodegenerative diseases by upregulating beneficial genes and downregulating harmful ones.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- The transcription factor tailless (TLX, NR2E1) is crucial for neuronal stem cell and retinal progenitor cell self-renewal.
- TLX is a master regulator of neurogenesis and a potential therapeutic target for neurodegenerative diseases.
Purpose of the Study:
- To develop highly potent and selective activators of TLX' transcriptional repressor activity.
- To investigate the transcriptomic effects of TLX activation.
Main Methods:
- Systematic extension and optimization of TLX ligands.
- RNA sequencing (RNAseq) to analyze transcriptomic changes.
- Assessing effects on genes related to cellular functions and neurodegeneration.
Main Results:
- Developed a TLX activator with nanomolar potency and high selectivity.
- Observed upregulation of genes involved in ATP production, lysosomal function, and vesicular transport.
- Induced PTEN-induced kinase 1 (PINK1) and downregulated beta-secretase (BACE), indicating anti-neurodegenerative potential.
Conclusions:
- TLX activators represent a promising therapeutic strategy for neurodegenerative conditions.
- TLX modulation influences key cellular processes and targets relevant to neurodegeneration at the transcriptional level.
Related Concept Videos
02:04Co-activators and Co-repressors
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...
02:04Co-activators and Co-repressors
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...
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...
01:58Prokaryotic Transcriptional Activators and Repressors
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
01:58Prokaryotic Transcriptional Activators and Repressors
The organization of prokaryotic genes in their genome is notably different from that of eukaryotes. Prokaryotic genes are organized, such that the genes for proteins involved in the same biochemical process or function are located together in groups. This group of genes, along with their regulatory elements, are collectively known as an operon. The functional genes in an operon are transcribed together to give a single strand of mRNA known as polycistronic mRNA.
Transcription of prokaryotic...
Transcription of prokaryotic...
01:42What is Gene Expression?
Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is made up of nucleotides and proteins consist of amino...