DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle

Abstract Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tis...

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Main Authors: Hideki Maehara, Toshiya Kokaji, Atsushi Hatano, Yutaka Suzuki, Masaki Matsumoto, Keiichi I. Nakayama, Riku Egami, Takaho Tsuchiya, Haruka Ozaki, Keigo Morita, Masaki Shirai, Dongzi Li, Akira Terakawa, Saori Uematsu, Ken-ichi Hironaka, Satoshi Ohno, Hiroyuki Kubota, Hiromitsu Araki, Fumihito Miura, Takashi Ito, Shinya Kuroda
Format: Article
Language:English
Published: Nature Portfolio 2023-11-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-023-46393-5
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author Hideki Maehara
Toshiya Kokaji
Atsushi Hatano
Yutaka Suzuki
Masaki Matsumoto
Keiichi I. Nakayama
Riku Egami
Takaho Tsuchiya
Haruka Ozaki
Keigo Morita
Masaki Shirai
Dongzi Li
Akira Terakawa
Saori Uematsu
Ken-ichi Hironaka
Satoshi Ohno
Hiroyuki Kubota
Hiromitsu Araki
Fumihito Miura
Takashi Ito
Shinya Kuroda
author_facet Hideki Maehara
Toshiya Kokaji
Atsushi Hatano
Yutaka Suzuki
Masaki Matsumoto
Keiichi I. Nakayama
Riku Egami
Takaho Tsuchiya
Haruka Ozaki
Keigo Morita
Masaki Shirai
Dongzi Li
Akira Terakawa
Saori Uematsu
Ken-ichi Hironaka
Satoshi Ohno
Hiroyuki Kubota
Hiromitsu Araki
Fumihito Miura
Takashi Ito
Shinya Kuroda
author_sort Hideki Maehara
collection DOAJ
description Abstract Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins.
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spelling doaj.art-98436c9b09ae438fad492d19430389912023-11-05T12:16:44ZengNature PortfolioScientific Reports2045-23222023-11-0113111910.1038/s41598-023-46393-5DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscleHideki Maehara0Toshiya Kokaji1Atsushi Hatano2Yutaka Suzuki3Masaki Matsumoto4Keiichi I. Nakayama5Riku Egami6Takaho Tsuchiya7Haruka Ozaki8Keigo Morita9Masaki Shirai10Dongzi Li11Akira Terakawa12Saori Uematsu13Ken-ichi Hironaka14Satoshi Ohno15Hiroyuki Kubota16Hiromitsu Araki17Fumihito Miura18Takashi Ito19Shinya Kuroda20Department of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoDepartment of Omics and Systems Biology, Graduate School of Medical and Dental Sciences, Niigata UniversityDepartment of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoBioinformatics Laboratory, Institute of Medicine, University of TsukubaBioinformatics Laboratory, Institute of Medicine, University of TsukubaDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDepartment of Biological Sciences, Graduate School of Science, The University of TokyoDivision of Integrated Omics, Medical Research Center for High Depth Omics, Medical Institute of Bioregulation, Kyushu UniversityDepartment of Biochemistry, Kyushu University Graduate School of Medical SciencesDepartment of Biochemistry, Kyushu University Graduate School of Medical SciencesDepartment of Biochemistry, Kyushu University Graduate School of Medical SciencesDepartment of Biological Sciences, Graduate School of Science, The University of TokyoAbstract Each tissue has a dominant set of functional proteins required to mediate tissue-specific functions. Epigenetic modifications, transcription, and translational efficiency control tissue-dominant protein production. However, the coordination of these regulatory mechanisms to achieve such tissue-specific protein production remains unclear. Here, we analyzed the DNA methylome, transcriptome, and proteome in mouse liver and skeletal muscle. We found that DNA hypomethylation at promoter regions is globally associated with liver-dominant or skeletal muscle-dominant functional protein production within each tissue, as well as with genes encoding proteins involved in ubiquitous functions in both tissues. Thus, genes encoding liver-dominant proteins, such as those involved in glycolysis or gluconeogenesis, the urea cycle, complement and coagulation systems, enzymes of tryptophan metabolism, and cytochrome P450-related metabolism, were hypomethylated in the liver, whereas those encoding-skeletal muscle-dominant proteins, such as those involved in sarcomere organization, were hypomethylated in the skeletal muscle. Thus, DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins.https://doi.org/10.1038/s41598-023-46393-5
spellingShingle Hideki Maehara
Toshiya Kokaji
Atsushi Hatano
Yutaka Suzuki
Masaki Matsumoto
Keiichi I. Nakayama
Riku Egami
Takaho Tsuchiya
Haruka Ozaki
Keigo Morita
Masaki Shirai
Dongzi Li
Akira Terakawa
Saori Uematsu
Ken-ichi Hironaka
Satoshi Ohno
Hiroyuki Kubota
Hiromitsu Araki
Fumihito Miura
Takashi Ito
Shinya Kuroda
DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
Scientific Reports
title DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
title_full DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
title_fullStr DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
title_full_unstemmed DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
title_short DNA hypomethylation characterizes genes encoding tissue-dominant functional proteins in liver and skeletal muscle
title_sort dna hypomethylation characterizes genes encoding tissue dominant functional proteins in liver and skeletal muscle
url https://doi.org/10.1038/s41598-023-46393-5
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