The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex

Dharmeshkumar Patel, Atsushi Shimomura, Sreeparna Majumdar, Matthew C. Holley, Eri Hashino

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

The histone demethylase LSD1 plays a pivotal role in cellular differentiation, particularly in silencing lineage-specific genes. However, little is known about how LSD1 regulates neurosensory differentiation in the inner ear. Here we show that LSD1 interacts directly with the transcription factor Pax2 to form the NuRD co-repressor complex at the Pax2 target gene loci in a mouse otic neuronal progenitor cell line (VOT-N33). VOT-N33 cells expressing a Pax2-response element reporter were GFP-negative when untreated, but became GFP positive after forced differentiation or treatment with a potent LSD inhibitor. Pharmacological inhibition of LSD1 activity resulted in the enrichment of mono- and di-methylation of H3K4, upregulation of sensory neuronal genes and an increase in the number of sensory neurons in mouse inner ear organoids. Together, these results identify the LSD1/NuRD complex as a previously unrecognized modulator for Pax2-mediated neuronal differentiation in the inner ear.

Original languageEnglish (US)
Article numbere0191689
JournalPLoS One
Volume13
Issue number1
DOIs
StatePublished - Jan 1 2018

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Mi-2 Nucleosome Remodeling and Deacetylase Complex
Histone Demethylases
Inner Ear
histones
ears
Methylation
Genes
Cells
Organoids
methylation
Co-Repressor Proteins
Lysergic Acid Diethylamide
Response Elements
Sensory Receptor Cells
Modulators
Neurons
Ear
genes
sensory neurons
response elements

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex. / Patel, Dharmeshkumar; Shimomura, Atsushi; Majumdar, Sreeparna; Holley, Matthew C.; Hashino, Eri.

In: PLoS One, Vol. 13, No. 1, e0191689, 01.01.2018.

Research output: Contribution to journalArticle

Patel, Dharmeshkumar ; Shimomura, Atsushi ; Majumdar, Sreeparna ; Holley, Matthew C. ; Hashino, Eri. / The histone demethylase LSD1 regulates inner ear progenitor differentiation through interactions with Pax2 and the NuRD repressor complex. In: PLoS One. 2018 ; Vol. 13, No. 1.
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