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PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1

The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way...

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Autores principales: Schneider, Lucas, Herkt, Stefanie, Wang, Lei, Feld, Christine, Wesely, Josephine, Kuvardina, Olga N., Meyer, Annekarin, Oellerich, Thomas, Häupl, Björn, Seifried, Erhard, Bonig, Halvard, Lausen, Joern
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129428/
https://www.ncbi.nlm.nih.gov/pubmed/34001852
http://dx.doi.org/10.1038/s41389-021-00332-z
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author Schneider, Lucas
Herkt, Stefanie
Wang, Lei
Feld, Christine
Wesely, Josephine
Kuvardina, Olga N.
Meyer, Annekarin
Oellerich, Thomas
Häupl, Björn
Seifried, Erhard
Bonig, Halvard
Lausen, Joern
author_facet Schneider, Lucas
Herkt, Stefanie
Wang, Lei
Feld, Christine
Wesely, Josephine
Kuvardina, Olga N.
Meyer, Annekarin
Oellerich, Thomas
Häupl, Björn
Seifried, Erhard
Bonig, Halvard
Lausen, Joern
author_sort Schneider, Lucas
collection PubMed
description The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy.
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spelling pubmed-81294282021-05-27 PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1 Schneider, Lucas Herkt, Stefanie Wang, Lei Feld, Christine Wesely, Josephine Kuvardina, Olga N. Meyer, Annekarin Oellerich, Thomas Häupl, Björn Seifried, Erhard Bonig, Halvard Lausen, Joern Oncogenesis Article The establishment of cell type specific gene expression by transcription factors and their epigenetic cofactors is central for cell fate decisions. Protein arginine methyltransferase 6 (PRMT6) is an epigenetic regulator of gene expression mainly through methylating arginines at histone H3. This way it influences cellular differentiation and proliferation. PRMT6 lacks DNA-binding capability but is recruited by transcription factors to regulate gene expression. However, currently only a limited number of transcription factors have been identified, which facilitate recruitment of PRMT6 to key cell cycle related target genes. Here, we show that LEF1 contributes to the recruitment of PRMT6 to the central cell cycle regulator CCND1 (Cyclin D1). We identified LEF1 as an interaction partner of PRMT6. Knockdown of LEF1 or PRMT6 reduces CCND1 expression. This is in line with our observation that knockdown of PRMT6 increases the number of cells in G1 phase of the cell cycle and decreases proliferation. These results improve the understanding of PRMT6 activity in cell cycle regulation. We expect that these insights will foster the rational development and usage of specific PRMT6 inhibitors for cancer therapy. Nature Publishing Group UK 2021-05-17 /pmc/articles/PMC8129428/ /pubmed/34001852 http://dx.doi.org/10.1038/s41389-021-00332-z Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Schneider, Lucas
Herkt, Stefanie
Wang, Lei
Feld, Christine
Wesely, Josephine
Kuvardina, Olga N.
Meyer, Annekarin
Oellerich, Thomas
Häupl, Björn
Seifried, Erhard
Bonig, Halvard
Lausen, Joern
PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title_full PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title_fullStr PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title_full_unstemmed PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title_short PRMT6 activates cyclin D1 expression in conjunction with the transcription factor LEF1
title_sort prmt6 activates cyclin d1 expression in conjunction with the transcription factor lef1
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129428/
https://www.ncbi.nlm.nih.gov/pubmed/34001852
http://dx.doi.org/10.1038/s41389-021-00332-z
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