Related Experiment Video
Updated: Aug 4, 2026

Promoter Capture Hi-C: High-resolution, Genome-wide Profiling of Promoter Interactions
Published on: June 28, 2018
Dimerization-induced corepressor binding and relaxed DNA-binding specificity are critical for PML/RARA-induced
Jun Zhou1, Laurent Pérès, Nicole Honoré
1Centre National de la Recherche Scientifique Unité Mixte de Recherche 7151, Université de Paris 7, Equipe labellisée par la Ligue Nationale contre le Cancer, Hôpital St. Louis, 1 Avenue C. Vellefaux, 75475 Paris Cedex 10, France.
Abstract:
The pathogenesis of acute promyelocytic leukemia involves the transcriptional repression of master genes of myeloid differentiation by the promyelocytic leukemia-retinoic acid receptor alpha (PML/RARA) oncogene. PML-enforced RARA homodimerization allows the tighter binding of corepressors, silencing RARA target genes. In addition, homodimerization dramatically extends the spectrum of DNA-binding sites of the fusion protein compared with those of normal RARA. Yet, any contribution of these two properties of PML/RARA to differentiation arrest and immortalization of primary mouse hematopoietic progenitors was unknown. We demonstrate that dimerization-induced silencing mediator of retinoid and thyroid receptors (SMRT)-enhanced binding and relaxed DNA-binding site specificity are both required for efficient immortalization. Thus, enforced RARA dimerization is critical not only for triggering transcriptional repression but also for extending the repertoire of target genes. Our studies exemplify how dimerization-induced gain of functions converts an unessential transcription factor into a dominant oncogenic protein.
Related Concept Videos
Negative Regulator Molecules
RNA Polymerase II Accessory Proteins
Cooperative Binding of Transcription Regulators
Co-activators and Co-repressors
Abnormal Proliferation
Chromatin Modification in iPS Cells
Compact chromatin makes reprogramming difficult. Enzymes, such as histone demethylases and acetyltransferases, are often added during reprogramming to loosen the chromatin, making the DNA more accessible to transcription factors. Molecules that inhibit histone...

