Bouchard, C.* ; Sahu, P.* ; Meixner, M.* ; Nötzold, R.R.* ; Rust, M.B.* ; Kremmer, E. ; Feederle, R. ; Hart-Smith, G.* ; Finkernagel, F.* ; Bartkuhn, M.* ; Savai Pullamsetti, S.* ; Nist, A.* ; Stiewe, T.* ; Philipsen, S.* ; Bauer, U.M.*
Genomic location of PRMT6-dependent H3R2 methylation is linked to the transcriptional outcome of associated genes.
Cell Rep. 24, 3339-3352 (2018)
Protein arginine methyltransferase 6 (PRMT6) catalyzes asymmetric dimethylation of histone H3 at arginine 2 (H3R2me2a). This mark has been reported to associate with silent genes. Here, we use a cell model of neural differentiation, which upon PRMT6 knockout exhibits proliferation and differentiation defects. Strikingly, we detect PRMT6-dependent H3R2me2a at active genes, both at promoter and enhancer sites. Loss of H3R2me2a from promoter sites leads to enhanced KMT2A binding and H3K4me3 deposition together with increased target gene transcription, supporting a repressive nature of H3R2me2a. At enhancers, H3R2me2a peaks co-localize with the active enhancer marks H3K4me1 and H3K27ac. Here, loss of H3R2me2a results in reduced KMT2D binding and H3K4me1/H3K27ac deposition together with decreased transcription of associated genes, indicating that H3R2me2a also exerts activation functions. Our work suggests that PRMT6 via H3R2me2a interferes with the deposition of adjacent histone marks and modulates the activity of important differentiation-associated genes by opposing transcriptional effects.
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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Typ der Hochschulschrift
Herausgeber
Schlagwörter
Chromatin ; Gene Expression ; Histone Arginine Methylation ; Histone Code ; Histone Modifications ; Neural Differentiation ; Pluripotency ; Posttranslational Modifications ; Protein Arginine Methyltransferases ; Transcriptional Regulation; Histone Arginine Methylation; Embryonal Carcinoma-cells; H3k4 Trimethylation; Tumor-suppressor; Prmt6; Expression; Differentiation; Repression; Senescence; Identity
Keywords plus
Sprache
englisch
Veröffentlichungsjahr
2018
Prepublished im Jahr
HGF-Berichtsjahr
2018
ISSN (print) / ISBN
2211-1247
e-ISSN
2211-1247
ISBN
Bandtitel
Konferenztitel
Konferzenzdatum
Konferenzort
Konferenzband
Quellenangaben
Band: 24,
Heft: 12,
Seiten: 3339-3352
Artikelnummer: ,
Supplement: ,
Reihe
Verlag
Cell Press
Verlagsort
50 Hampshire St, Floor 5, Cambridge, Ma 02139 Usa
Tag d. mündl. Prüfung
0000-00-00
Betreuer
Gutachter
Prüfer
Topic
Hochschule
Hochschulort
Fakultät
Veröffentlichungsdatum
0000-00-00
Anmeldedatum
0000-00-00
Anmelder/Inhaber
weitere Inhaber
Anmeldeland
Priorität
Begutachtungsstatus
Peer reviewed
POF Topic(s)
30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
30201 - Metabolic Health
Forschungsfeld(er)
Immune Response and Infection
Helmholtz Diabetes Center
PSP-Element(e)
G-501793-001
G-502210-001
Förderungen
Copyright
Erfassungsdatum
2018-09-26