RXR heterodimers orchestrate transcriptional control of neurogenesis and cell fate specification

Zoltan Simandi, Attila Horvath, Ixchelt Cuaranta-Monroy, Sascha Sauer, Jean Francois Deleuze, Laszlo Nagy

Research output: Contribution to journalArticle

Abstract

Retinoid X Receptors (RXRs) are unique and enigmatic members of the nuclear receptor (NR) family with extensive and complex biological functions in cellular differentiation. On the one hand, RXRs through permissive heterodimerization with other NRs are able to integrate multiple lipid signaling pathways and are believed to play a central role to coordinate the development of the central nervous system. On the other hand, RXRs may have heterodimer-independent functions as well. Therefore, a more RXR-centric analysis is warranted to identify its genomic binding sites and regulated gene networks, which are orchestrating the earliest events in neuronal differentiation. Recently developed genome-wide approaches allow systematic analyses of the RXR-driven neural differentiation. Here we applied next generation sequencing-based methodology to track the dynamic redistribution of the RXR cistrome along the path of embryonic stem cell to glutamatergic neuron differentiation. We identified Retinoic Acid Receptor (RAR) and Liver X Receptor (LXR) as dominant heterodimeric partners of RXR in these cellular stages. Our data presented here characterize the RAR:RXR and LXR:RXR-mediated transcriptional program in embryonic stem cells, neural progenitors and terminally differentiated neurons. Considering the growing evidence for dysregulated RXR-mediated signaling in neurodegenerative disorders, such as Alzheimer's Disease or Amyotrophic Lateral Sclerosis, the data presented here will be also a valuable resource for the field of neuro(patho)biology.

Original languageEnglish (US)
Pages (from-to)51-62
Number of pages12
JournalMolecular and Cellular Endocrinology
Volume471
DOIs
StatePublished - Aug 15 2018
Externally publishedYes

Keywords

  • Hox
  • LXR
  • Neurodegeneration
  • Neurogenesis
  • Neuron
  • RAR
  • RXR

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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