Related Experiment Video
Updated: Jun 27, 2026
09:16
Investigation of the Transcriptional Role of a RUNX1 Intronic Silencer by CRISPR/Cas9 Ribonucleoprotein in Acute Myeloid Leukemia Cells
Published on: September 1, 2019
Transcriptional ERRgamma2-mediated activation is regulated by sentrin-specific proteases
Moritz Hentschke1, Ute Süsens, Uwe Borgmeyer
1Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
The Biochemical Journal
|December 11, 2008
Summary
Sumoylation, a modification of transcription factors, can repress their activity. This study shows reversible phosphorylation-dependent sumoylation regulates oestrogen receptor-related receptor gamma (ERRgamma) activity.
Area of Science:
- Molecular Biology
- Gene Regulation
- Nuclear Receptor Signaling
Background:
- Sumoylation is a key regulatory mechanism for transcription factors, often leading to repression.
- Oestrogen receptor-related receptor gamma (ERRgamma) is a constitutively active orphan nuclear receptor involved in various cellular processes.
- The N-terminus of ERRgamma2 contains an activation function (AF-1) near a phosphorylation-dependent sumoylation motif (PDSM).
Purpose of the Study:
- To investigate the role of sumoylation and phosphorylation in regulating ERRgamma activity.
- To elucidate the mechanism by which sumoylation affects ERRgamma function.
- To identify the specific motifs and residues involved in ERRgamma sumoylation and its regulation.
Main Methods:
- Mutational analysis of ERRgamma2 to identify key residues and motifs.
- Electrophoretic mobility-shift assay (EMSA) to visualize phosphorylation.
- Co-expression studies with co-activators (PGC-1beta) and proteases (sentrin/SENP family members).
Main Results:
- Sumoylation of lysine 40 in ERRgamma2, regulated by phosphorylation, modulates its activity.
- Phosphorylation at the +5 position relative to the sumoylation site was visualized by EMSA.
- Sumoylation represses ERRgamma activity, and this repression can be reversed by sentrin/SENP proteases.
- The PDSM functions as a repression function (RF-1) for the adjacent AF-1.
Conclusions:
- Reversible phosphorylation-dependent sumoylation is a novel mechanism for regulating orphan nuclear receptor activity.
- ERRgamma activity is finely tuned through a dynamic interplay between phosphorylation and sumoylation.
- This regulatory mechanism offers potential targets for therapeutic interventions in diseases involving ERRgamma signaling.
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...
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...
02:23Master 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...
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...
01:42What 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...
01:36What is Gene Expression?
A gene is a stretch of DNA that serves as the blueprint for functional RNAs and proteins. Since DNA is comprised of nucleotides and proteins are comprised of amino acids, a mediator is required to convert the information encoded in DNA into proteins. This mediator is the messenger RNA (mRNA). mRNA copies the blueprint from DNA by a process called transcription. In eukaryotes, transcription occurs in the nucleus by complementary base-pairing with the DNA template. The mRNA is then processed and...