Identification of myelin transcription factor 1 (MyT1) as a subunit of the neural cell type-specific lysine-specific demethylase 1 (LSD1) complex

Atsushi Yokoyama, Katsuhide Igarashi, Tetsuya Sato, Kiyoshi Takagi, Maky I. Otsuka, Yurina Shishido, Takashi Baba, Ryo Ito, Jun Kanno, Yasuyuki Ohkawa, Ken Ichirou Morohashi, Akira Sugawara

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Regulation of spatiotemporal gene expression in higher eukaryotic cells is critical for the precise and orderly development of undifferentiated progenitors into committed cell types of the adult. It is well known that dynamic epigenomic regulation (including chromatin remodeling and histone modifications by transcriptional coregulator complexes) is involved in transcriptional regulation. Precisely how these coregulator complexes exert their cell type and developing stage-specific activity is largely unknown. In this study we aimed to isolate the histone demethylase lysine-specific demethylase 1 (LSD1) complex from neural cells by biochemical purification. In so doing, we identified myelin transcription factor 1 (MyT1) as a novel LSD1 complex component. MyT1 is a neural cell-specific zinc finger factor, and it forms a stable multiprotein complex with LSD1 through direct interaction. Target gene analysis using microarray and ChIP assays revealed that the Pten gene was directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1orMyT1 derepressed the expressionofendogenous target genes and inhibited cell proliferation of a neuroblastoma cell line, Neuro2a. We propose that formation of tissue-specific combinations of coregulator complexes is a critical mechanism for tissue-specific transcriptional regulation.

Original languageEnglish
Pages (from-to)18152-18162
Number of pages11
JournalJournal of Biological Chemistry
Volume289
Issue number26
DOIs
Publication statusPublished - 2014 Jun 27

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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