Release Date: 20 May 2014

Identification of Myt1 as a subunit of the neural cell type-specific LSD1 complex

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  • Atsushi Yokoyama
    Atsushi Yokoyama
    Email: geo@ncbi.nlm.nih.gov
    Role: submitter
    Affiliation: Tohoku University Graduate School of Medicine
    1
  • Katsuhide Igarashi
    Katsuhide Igarashi
  • Tetsuya Sato
    Tetsuya Sato
  • Kiyoshi Takagi
    Kiyoshi Takagi
  • Maky Otsuka I.
    Maky Otsuka I.
  • Yurina Shishido
    Yurina Shishido
  • Takashi Baba
    Takashi Baba
  • Ryo Ito
    Ryo Ito
  • Jun Kanno
    Jun Kanno
  • Yasuyuki Ohkawa
    Yasuyuki Ohkawa
  • + 2 more
  • 1 Tohoku University Graduate School of Medicine
    Address: Tohoku University Graduate School of Medicine, seiryo-machi 2-1, Aoba-ku, Sendai, Sendai, Miyagi, Japan
AccessionE-GEOD-49685
Study typetranscription profiling by array
OrganismMus musculus
DescriptionRegulation 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. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be 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 LSD1 complex from neural cells by biochemical purification. In so doing, we identified 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 several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous 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. Neuro2a cells were treated with either siControl, siLSD1 or siMyT1 for 48 h (n=3)
Publication Yokoyama A, Igarashi K, Sato T, Takagi K, I MO, Shishido Y, Baba T, Ito R, Kanno J, Ohkawa Y, Morohashi KI, Sugawara A. Identification of myelin transcription factor 1 (MyT1) as a Subunit of the Neural Cell Type-specific Lysine-specific demethylase 1 (LSD1) Complex. doi 10.1074/jbc.M114.566448 PMID 24828497 DOI 10.1074/jbc.M114.566448
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. Recently, dynamic epigenomic regulation, including chromatin remodeling and histone modifications by transcriptional coregulator complexes, has been shown to be 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 LSD1 complex from neural cells by biochemical purification. In so doing, we identified 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 several genes, including PTEN, that were directly regulated by the LSD1-MyT1 complex. Knockdown of either LSD1 or MyT1 derepressed the expression of endogenous 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. Neuro2a cells were treated with either siControl, siLSD1 or siMyT1 for 48 h (n=3)
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Samples
Sample count9
Experimental Factorstreatment
Experimental Factors
Source Characteristics
Assays and Data
Assay count9
TechnologyArray assay
Assay by MoleculeRNA assay
Raw Data
Processed Data
MAGE-TAB Files
Array Designs 1 link
MIAME Score
Platforms-
Variables*
Processed*
Protocols*
Raw*