Related Experiment Video

Updated: Apr 23, 2026

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1
11:02

Methods to Discover Alternative Promoter Usage and Transcriptional Regulation of Murine Bcrp1

Published on: May 27, 2016

7.6K

Clearance of PML/RARA-bound promoters suffice to initiate APL differentiation

Adeline Vitaliano-Prunier1, Juliane Halftermeyer1, Julien Ablain1

  • 1Université Paris Diderot, Sorbonne Paris Cité, Paris, France; INSERM Unité Mixte de Recherche 944, Equipe Labellisée par la Ligue Nationale contre le Cancer, Institut Universitaire d'Hématologie, Paris, France; Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7212, Hôpital St. Louis, Paris, France;

Blood
|September 27, 2014
PubMed

Insights

Acute promyelocytic leukemia (APL) differentiation is triggered by removing the PML/RARA oncoprotein, not by active gene activation. Clearing PML/RARA from DNA allows myeloid differentiation, explaining arsenic

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Hematology

Background:

  • The PML/RARA oncoprotein drives acute promyelocytic leukemia (APL) by inhibiting myeloid differentiation.
  • Retinoid X receptor-alpha (RXRA) binding to PML/RARA is crucial for its oncogenic function and DNA binding.
  • APL cells are sensitive to retinoic acid (RA) and arsenic trioxide, which induce differentiation.

Purpose of the Study:

  • To elucidate the mechanism by which arsenic trioxide induces APL cell differentiation.
  • To investigate the role of PML/RARA clearance and retinoid X receptors in APL pathogenesis and differentiation.

Main Methods:

  • Investigated the effect of PML/RARA extinction on myeloid differentiation in vivo.
  • Examined the impact of retinoid X receptor ablation on PML/RARA DNA binding and APL cell differentiation ex vivo and in vivo.
  • Assessed the role of RXRA sumoylation in PML/RARA-mediated transformation.

Main Results:

  • PML/RARA extinction triggers terminal myeloid differentiation in vivo.
  • Ablation of retinoid X receptors disrupts PML/RARA DNA binding, inducing APL cell differentiation.
  • RXRA sumoylation enhances PML/RARA's transcriptional repression and oncogenic transformation.

Conclusions:

  • APL differentiation is a default program initiated by the clearance of PML/RARA from target gene promoters.
  • Arsenic induces APL maturation by promoting PML/RARA degradation, leading to the release of repressed myeloid differentiation genes.
  • Targeting PML/RARA clearance offers a therapeutic strategy for APL.

More Related Videos

Massively Parallel Reporter Assays in Cultured Mammalian Cells11:03

Massively Parallel Reporter Assays in Cultured Mammalian Cells

Published on: August 17, 2014

23.3K
Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions10:16

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions

Published on: June 28, 2018

34.4K

Related Concept Videos

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...
8.8K
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...
6.0K
The Eukaryotic Promoter Region02:40

The 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...
16.1K
Abnormal Proliferation02:23

Abnormal Proliferation

Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the...
4.0K