Identification of Myelin Transcription Factor 1 (MyT1) as a Subunit of the Neural Cell Type-specific Lysine-specific Demethylase 1 (LSD1) Complex

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

doi:10.1074/jbc.m114.566448

Cited by 37 publications

(46 citation statements)

References 65 publications

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“…Previous work in Neuro2a neuroblastoma cells with knock-down of Myt1 identified a list of genes that were altered on reduction of endogenous Myt1 expression. 18 Comparison of our data to this data-set revealed a relatively small overlap, although this is perhaps not surprising, given the different cell types and different analysis platforms (expression array versus RNA-seq). However, within the overlap between our Myt1 data and that from the knock-down the majority of genes had reduced expression in our Myt1 expressing cells and increased expression in the Myt1 knockdown analysis ( Figure 6A).…”

Section: Myt1l Expressing Cellsmentioning

confidence: 69%

Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors

Manukyan

Kowalczyk

Melhuish

et al. 2018

J of Cellular Biochemistry

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Myt1 and Myt1l (Myelin transcription factor 1, and Myt1-like) are members of a small family of closely related zinc finger transcription factors, characterized by two clusters of C2HC zinc fingers. Both are widely expressed during early embryogenesis, but are largely restricted to expression within the brain in the adult. Myt1l, as part of a three transcription factor mix, can reprogram fibroblasts to neurons and plays a role in maintaining neuronal identity. Previous analyses have indicated roles in both transcriptional activation and repression and suggested that Myt1 and Myt1l may have opposing functions in gene expression. We show that when targeted to DNA via multiple copies of the consensus Myt1/Myt1l binding site Myt1 represses transcription, whereas Myt1l activates. By targeting via a heterologous DNA binding domain we mapped an activation function in Myt1l to an amino-terminal region that is poorly conserved in Myt1. However, genome wide analyses of the effects of Myt1 and Myt1l expression in a glioblastoma cell line suggest that the two proteins have largely similar effects on endogenous gene expression. Transcriptional repression is likely mediated by binding to DNA via the known consensus site, whereas this site is not associated with the transcriptional start sites of genes with higher expression in the presence of Myt1 or Myt1l. This work suggests that these two proteins function similarly, despite differences observed in analyses based on synthetic reporter constructs.

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Section: Myt1l Expressing Cellsmentioning

confidence: 69%

Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors

Manukyan

Kowalczyk

Melhuish

et al. 2018

J of Cellular Biochemistry

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“…All three genes are predominantly expressed in developing mammalian neural tissues 25. MYT1 is part of the lysine-specific demethylase 1 complex that plays a crucial role in the neural cell-specific regulation of gene expression 26. In Xenopus laevis , Myt1 was involved in primary selection of neuronal precursor cells, acting synergistically with neurogenin-1 in the Notch signalling pathway and allowing cells to escape lateral inhibition 27 28.…”

Section: Discussionmentioning

confidence: 99%

Mutations inMYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS

et al. 2016

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“…Then, they confirmed that the LSD1 complex directly bound to the PTEN (phosphatase and tensin homolog) gene promoter through MyT1 protein and demethylated H3K4me2 at its promoter. The Neuro2a‐cell proliferation was then decreased, due to downregulation of either Myt1 or LSD1 expression …”

Section: Biochemistry Of Lsd1mentioning

confidence: 99%

“…The Neuro2a-cell proliferation was then decreased, due to downregulation of either Myt1 or LSD1 expression. 64 Epithelial-mesenchymal transition (EMT) has been demonstrated to play pivotal roles during embryonic development and carcinoma progression. Lin et al showed that LSD1 was essential for Snail1-mediated transcriptional repression and for maintenance of the silenced state of Snail target genes in invasive cancer cells.…”

Section: Nonhistone Substrates Of Lsd1 and Protein-protein Interacmentioning

confidence: 99%

A Systematic Review of Histone Lysine‐Specific Demethylase 1 and Its Inhibitors

Zheng¹,

Wang²,

Li³

et al. 2015

Medicinal Research Reviews

164

130

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Histone lysine-specific demethylase 1 (LSD1) is the first discovered and reported histone demethylase by Dr. Shi Yang's group in 2004. It is classified as a member of amine oxidase superfamily, the common feature of which is using the flavin adenine dinucleotide (FAD) as its cofactor. Since it is located in cell nucleus and acts as a histone methylation eraser, LSD1 specifically removes mono- or dimethylated histone H3 lysine 4 (H3K4) and H3 lysine 9 (H3K9) through formaldehyde-generating oxidation. It has been indicated that LSD1 and its downstream targets are involved in a wide range of biological courses, including embryonic development and tumor-cell growth and metastasis. LSD1 has been reported to be overexpressed in variety of tumors. Inactivating LSD1 or downregulating its expression inhibits cancer-cell development. LSD1 targeting inhibitors may represent a new insight in anticancer drug discovery. This review summarizes recent studies about LSD1 and mainly focuses on the basic physiological function of LSD1 and its involved mechanisms in pathophysiologic conditions, as well as the development of LSD1 inhibitors as potential anticancer therapeutic agents.

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Identification of Myelin Transcription Factor 1 (MyT1) as a Subunit of the Neural Cell Type-specific Lysine-specific Demethylase 1 (LSD1) Complex

Cited by 37 publications

References 65 publications

Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors

Analysis of transcriptional activity by the Myt1 and Myt1l transcription factors

Mutations inMYT1, encoding the myelin transcription factor 1, are a rare cause of OAVS

A Systematic Review of Histone Lysine‐Specific Demethylase 1 and Its Inhibitors

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