Related Experiment Video

Updated: Sep 15, 2025

Inducible and Reversible Dominant-negative DN Protein Inhibition
08:35

Inducible and Reversible Dominant-negative DN Protein Inhibition

Published on: January 7, 2019

8.5K

Non-canonical activating roles of RCoR2 sustain transcription in adrenergic neuroblastoma

Sara Aloisi1, Martina Santulli1, Marco Russo2

  • 1Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy.

Cell Reports
|July 15, 2025
PubMed

Insights

The study reveals RCoR2, a component of CoREST complexes, plays a novel positive role in gene regulation in neuroblastoma (NB). This finding identifies RCoR2 as a potential therapeutic target for high-risk NB cancers.

Area of Science:

  • Epigenetics and Gene Regulation
  • Cancer Biology
  • Neuro-oncology

Background:

  • CoREST complexes, including LSD1, HDAC1/2, and RCoR1/2/3, are crucial for neurodevelopment and cancer.
  • The specific roles of RCoR paralogs, particularly RCoR2, in cancer remain largely uncharacterized.

Purpose of the Study:

  • To investigate the non-canonical functions of RCoR2 in MYCN-amplified neuroblastoma (NB).
  • To elucidate the role of RCoR2 in regulating the NB chromatin landscape and gene expression.

Main Methods:

  • Analysis of RCoR2's role in MYCN-amplified neuroblastoma.
  • Investigating RCoR2 as a super-enhancer-driven gene.
  • Examining RCoR2's interaction with the core regulatory circuitry (CRC) in NB.

Main Results:

  • RCoR2 exhibits non-canonical functions in MYCN-amplified neuroblastoma, distinct from its paralogs.
  • RCoR2 is a super-enhancer-driven gene that positively regulates gene expression.
  • RCoR2 acts as a partner of the adrenergic NB core regulatory circuitry (CRC), facilitating enhancer-promoter interactions.

Conclusions:

  • RCoR2 is a key determinant of the NB chromatin landscape and a positive regulator of gene expression.
  • RCoR2 sustains the expression of genes vital for neuroblastoma cell survival.
  • RCoR2 represents a critical vulnerability and a promising therapeutic target in high-risk neuroblastomas.
Keywords:
CP: CancerCP: Molecular biologyCoRESTHDACLSD1MYCNRCOR1RCOR2adrenergiccore regulatory circuitryneuroblastomapediatric cancer

More Related Videos

Modeling Paracrine Noncanonical Wnt Signaling In Vitro11:14

Modeling Paracrine Noncanonical Wnt Signaling In Vitro

Published on: December 10, 2021

1.7K
Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation09:07

Prediction and Validation of Gene Regulatory Elements Activated During Retinoic Acid Induced Embryonic Stem Cell Differentiation

Published on: June 21, 2016

8.3K

Related Concept Videos

mTOR Signaling and Cancer Progression03:03

mTOR Signaling and Cancer Progression

The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
3.9K
Co-activators and Co-repressors02:04

Co-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...
7.6K
RNA Polymerase II Accessory Proteins02:36

RNA 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...
9.5K
Master Transcription Regulators02:23

Master 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...
7.1K
MAPK Signaling Cascades01:07

MAPK Signaling Cascades

Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.1K
Transducer Mechanism: Nuclear Receptors01:31

Transducer Mechanism: Nuclear Receptors

Nuclear receptors, or NRs, are unique transcription factors that regulate gene transcription and affect the cellular pathways involved in reproduction, development, or metabolism. Their ability to be stimulated by small lipophilic ligands and control vital cellular processes makes them ideal drug targets. Nearly 10-15% of currently prescribed drugs target these receptors.
About 48 different soluble family members of nuclear receptors are identified that can be divided into two main classes:
1.7K