PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology

Zoltan Simandi, Erik Czipa, Attila Horvath, Aron Koszeghy, Csilla Bordas, Szilárd Põliska, István Juhász, Lászlõ Imre, Gábor Szabõ, Balazs Dezso, Endre Barta, Sascha Sauer, Katalin Karolyi, Ilona Kovacs, Gábor Hutõczki, Lászlõ Bognár, Álmos Klekner, Peter Szucs, Bálint L. Bálint, Laszlo Nagy

Research output: Article

24 Citations (Scopus)

Abstract

Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects are mediated by RAR and RXR nuclear receptors. However, transcriptional cofactors required for cell and gene-specific retinoid signaling are not known. Here we show that protein arginine methyl transferase (PRMT) 1 and 8 have key roles in determining retinoid regulated gene expression and cellular specification in a multistage neuronal differentiation model of murine ESCs. PRMT1 acts as a selective modulator, providing the cells with a mechanism to reduce the potency of retinoid signals on regulatory "hotspots." PRMT8 is a retinoid receptor target gene itself and acts as a cell type specific transcriptional coactivator of retinoid signaling at later stages of differentiation. Lack of either of them leads to reduced nuclear arginine methylation, dysregulated neuronal gene expression, and altered neuronal activity. Importantly, depletion of PRMT8 results in altered expression of a distinct set of genes, including markers of gliomagenesis. PRMT8 is almost entirely absent in human glioblastoma tissues. We propose that PRMT1 and PRMT8 serve as a rheostat of retinoid signaling to determine neuronal cell specification in a context-dependent manner and might also be relevant in the development of human brain malignancy. Stem Cells 2015;33:726-741

Original languageEnglish
Pages (from-to)726-741
Number of pages16
JournalStem Cells
Volume33
Issue number3
DOIs
Publication statusPublished - márc. 1 2015

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Retinoids
Tretinoin
Embryonic Stem Cells
Arginine
Genes
Gene Expression
Human Development
Glioblastoma
Cytoplasmic and Nuclear Receptors
Transferases
Neuropathology
Methylation
Stem Cells
Neurons
Brain
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Medicine

Cite this

PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology. / Simandi, Zoltan; Czipa, Erik; Horvath, Attila; Koszeghy, Aron; Bordas, Csilla; Põliska, Szilárd; Juhász, István; Imre, Lászlõ; Szabõ, Gábor; Dezso, Balazs; Barta, Endre; Sauer, Sascha; Karolyi, Katalin; Kovacs, Ilona; Hutõczki, Gábor; Bognár, Lászlõ; Klekner, Álmos; Szucs, Peter; Bálint, Bálint L.; Nagy, Laszlo.

In: Stem Cells, Vol. 33, No. 3, 01.03.2015, p. 726-741.

Research output: Article

Simandi, Z, Czipa, E, Horvath, A, Koszeghy, A, Bordas, C, Põliska, S, Juhász, I, Imre, L, Szabõ, G, Dezso, B, Barta, E, Sauer, S, Karolyi, K, Kovacs, I, Hutõczki, G, Bognár, L, Klekner, Á, Szucs, P, Bálint, BL & Nagy, L 2015, 'PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology', Stem Cells, vol. 33, no. 3, pp. 726-741. https://doi.org/10.1002/stem.1894
Simandi Z, Czipa E, Horvath A, Koszeghy A, Bordas C, Põliska S et al. PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology. Stem Cells. 2015 márc. 1;33(3):726-741. https://doi.org/10.1002/stem.1894
Simandi, Zoltan ; Czipa, Erik ; Horvath, Attila ; Koszeghy, Aron ; Bordas, Csilla ; Põliska, Szilárd ; Juhász, István ; Imre, Lászlõ ; Szabõ, Gábor ; Dezso, Balazs ; Barta, Endre ; Sauer, Sascha ; Karolyi, Katalin ; Kovacs, Ilona ; Hutõczki, Gábor ; Bognár, Lászlõ ; Klekner, Álmos ; Szucs, Peter ; Bálint, Bálint L. ; Nagy, Laszlo. / PRMT1 and PRMT8 regulate retinoic acid-dependent neuronal differentiation with implications to neuropathology. In: Stem Cells. 2015 ; Vol. 33, No. 3. pp. 726-741.
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AU - Bordas, Csilla

AU - Põliska, Szilárd

AU - Juhász, István

AU - Imre, Lászlõ

AU - Szabõ, Gábor

AU - Dezso, Balazs

AU - Barta, Endre

AU - Sauer, Sascha

AU - Karolyi, Katalin

AU - Kovacs, Ilona

AU - Hutõczki, Gábor

AU - Bognár, Lászlõ

AU - Klekner, Álmos

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