Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity

Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity

Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on...

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Main Authors: Ishimoto, Kenji, Kawamata, Natsuko, Uchihara, Yoshie, Okubo, Moeka, Fujimoto, Reiko, Gotoh, Eiko, Kakinouchi, Keisuke, Mizohata, Eiichi, Hino, Nobumasa, Okada, Yoshiaki, Mochizuki, Yasuhiro, Tanaka, Toshiya, Hamakubo, Takao, Sakai, Juro, Kodama, Tatsuhiko, Inoue, Tsuyoshi, Tachibana, Keisuke, Doi, Takefumi
Format: Online
Language:English
Published: Public Library of Science 2016
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087952/
id pubmed-5087952
recordtype oai_dc
spelling pubmed-50879522016-11-15 Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity Ishimoto, Kenji Kawamata, Natsuko Uchihara, Yoshie Okubo, Moeka Fujimoto, Reiko Gotoh, Eiko Kakinouchi, Keisuke Mizohata, Eiichi Hino, Nobumasa Okada, Yoshiaki Mochizuki, Yasuhiro Tanaka, Toshiya Hamakubo, Takao Sakai, Juro Kodama, Tatsuhiko Inoue, Tsuyoshi Tachibana, Keisuke Doi, Takefumi Research Article Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1. Using mass spectrometry analysis, we show that the C-terminal region of human SETDB1 purified from insect cells is ubiquitinated. We also demonstrate that the ubiquitination of lysine 867 of the human SETDB1 is necessary for full H3K9 methyltransferase activity in mammalian cells. Finally, we show that SETDB1 ubiquitination regulates the expression of its target gene, serpin peptidase inhibitor, clade E, member 1 (SERPINE1) by methylating H3K9. These results suggest that the ubiquitination of SETDB1 at lysine 867 controls the expression of its target gene by activating its H3K9 methyltransferase activity. Public Library of Science 2016-10-31 /pmc/articles/PMC5087952/ /pubmed/27798683 http://dx.doi.org/10.1371/journal.pone.0165766 Text en © 2016 Ishimoto et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Ishimoto, Kenji
Kawamata, Natsuko
Uchihara, Yoshie
Okubo, Moeka
Fujimoto, Reiko
Gotoh, Eiko
Kakinouchi, Keisuke
Mizohata, Eiichi
Hino, Nobumasa
Okada, Yoshiaki
Mochizuki, Yasuhiro
Tanaka, Toshiya
Hamakubo, Takao
Sakai, Juro
Kodama, Tatsuhiko
Inoue, Tsuyoshi
Tachibana, Keisuke
Doi, Takefumi
spellingShingle Ishimoto, Kenji
Kawamata, Natsuko
Uchihara, Yoshie
Okubo, Moeka
Fujimoto, Reiko
Gotoh, Eiko
Kakinouchi, Keisuke
Mizohata, Eiichi
Hino, Nobumasa
Okada, Yoshiaki
Mochizuki, Yasuhiro
Tanaka, Toshiya
Hamakubo, Takao
Sakai, Juro
Kodama, Tatsuhiko
Inoue, Tsuyoshi
Tachibana, Keisuke
Doi, Takefumi
Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
author_facet Ishimoto, Kenji
Kawamata, Natsuko
Uchihara, Yoshie
Okubo, Moeka
Fujimoto, Reiko
Gotoh, Eiko
Kakinouchi, Keisuke
Mizohata, Eiichi
Hino, Nobumasa
Okada, Yoshiaki
Mochizuki, Yasuhiro
Tanaka, Toshiya
Hamakubo, Takao
Sakai, Juro
Kodama, Tatsuhiko
Inoue, Tsuyoshi
Tachibana, Keisuke
Doi, Takefumi
author_sort Ishimoto, Kenji
title Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
title_short Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
title_full Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
title_fullStr Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
title_full_unstemmed Ubiquitination of Lysine 867 of the Human SETDB1 Protein Upregulates Its Histone H3 Lysine 9 (H3K9) Methyltransferase Activity
title_sort ubiquitination of lysine 867 of the human setdb1 protein upregulates its histone h3 lysine 9 (h3k9) methyltransferase activity
description Posttranslational modifications (PTMs) of proteins play a crucial role in regulating protein-protein interactions, enzyme activity, subcellular localization, and stability of the protein. SET domain, bifurcated 1 (SETDB1) is a histone methyltransferase that regulates the methylation of histone H3 on lysine 9 (H3K9), gene silencing, and transcriptional repression. The C-terminal region of SETDB1 is a key site for PTMs, and is essential for its enzyme activity in mammalian and insect cells. In this study, we aimed to evaluate more precisely the effect of PTMs on the H3K9 methyltransferase activity of SETDB1. Using mass spectrometry analysis, we show that the C-terminal region of human SETDB1 purified from insect cells is ubiquitinated. We also demonstrate that the ubiquitination of lysine 867 of the human SETDB1 is necessary for full H3K9 methyltransferase activity in mammalian cells. Finally, we show that SETDB1 ubiquitination regulates the expression of its target gene, serpin peptidase inhibitor, clade E, member 1 (SERPINE1) by methylating H3K9. These results suggest that the ubiquitination of SETDB1 at lysine 867 controls the expression of its target gene by activating its H3K9 methyltransferase activity.
publisher Public Library of Science
publishDate 2016
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5087952/
_version_ 1613705645421232128

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