Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation

被引：47

作者：

Cheng, Hao ^{[1
,2
]}

Xuan, Hongwen ^{[1
,2
]}

Green, Christopher D. ^{[1
]}

Han, Yixing ^{[1
]}

Sun, Na ^{[1
]}

Shen, Hongjie ^{[3
,4
,5
,6
]}

McDermott, Joseph ^{[1
]}

Bennett, David A. ^{[7
]}

Lan, Fei ^{[3
,4
,5
,6
]}

Han, Jing-Dong J. ^{[1
]}

机构：

[1] Chinese Acad Sci, Collaborat Innovat Ctr Genet & Dev Biol, Max Planck Partner Inst Computat Biol,Key Lab Com, Shanghai Inst Nutr & Hlth,Shanghai Inst Biol Sci, Shanghai 200031, Peoples R China

[2] Univ Chinese Acad Sci, Beijing 100049, Peoples R China

[3] Fudan Univ, Zhongshan Hosp, Liver Canc Inst, Shanghai 200032, Peoples R China

[4] Fudan Univ, Minist Educ, Key Lab Carcinogenesis & Canc Invas, Shanghai 200032, Peoples R China

[5] Fudan Univ, Minist Sci & Technol, Key Lab Epigenet & Metab, Shanghai 200032, Peoples R China

[6] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China

[7] Rush Univ, Med Ctr, Rush Alzheimers Dis Ctr, Chicago, IL 60612 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2018年 / 115卷 / 29期

基金：

中国国家自然科学基金; 美国国家卫生研究院;

关键词：

inflammation; aging; brain; H3K27ac; gene-body acetylation; NF-KAPPA-B; ELEGANS LIFE-SPAN; C; ELEGANS; DEPENDENT MANNER; SUPER-ENHANCERS; EXPRESSION; DEACETYLATION; INHIBITION; ELONGATION; GENOME;

D O I：

10.1073/pnas.1800656115

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Brain "inflammaging," a low-grade and chronic inflammation, is a major hallmark for aging-related neurodegenerative diseases. Here, by profiling H3K27ac and gene expression patterns in human and mouse brains, we found that age-related up-regulated (Age-Up) and down-regulated (Age-Down) genes have distinct H3K27ac patterns. Although both groups show promoter H3K27ac, the Age-Up genes, enriched for inflammation-related functions, are additionally marked by broad H3K27ac distribution over their gene bodies, which is progressively reduced during aging. Age-related gene expression changes can be predicted by gene-body H3K27ac level. Contrary to the presumed transcription activation function of promoter H3K27ac, we found that broad gene-body hyper H3K27ac suppresses overexpression of inflammaging genes. Altogether, our findings revealed opposite regulations by H3K27ac of Age-Up and Age-Down genes and a mode of broad gene-body H3K27ac in repressing transcription.

引用

页码：7611 / 7616

页数：6

共 39 条

[1] Motif module map reveals enforcement of aging by continual NF-κB activity [J].

Adler, Adam S. ;

Sinha, Saurabh ;

Kawahara, Tiara L. A. ;

Zhang, Jennifer Y. ;

Segal, Eran ;

Chang, Howard Y. .

GENES & DEVELOPMENT, 2007, 21 (24) :3244-3257

[2] HDAC inhibitor-dependent transcriptome and memory reinstatement in cognitive decline models [J].

Benito, Eva ;

Urbanke, Hendrik ;

Ramachandran, Binu ;

Barth, Jonas ;

Haider, Rashi ;

Awasthi, Ankit ;

Jain, Gaurav ;

Capece, Vincenzo ;

Burkhardt, Susanne ;

Navarro-Sala, Magdalena ;

Nagarajan, Sankari ;

Schuetz, Anna-Lena ;

Johnsen, Steven A. ;

Bonn, Stefan ;

Luehrmann, Reinhardt ;

Dean, Camin ;

Fischer, Andre .

JOURNAL OF CLINICAL INVESTIGATION, 2015, 125 (09) :3572-3584

[3] IKK/NF-κB and STAT3 pathways: central signalling hubs in inflammation-mediated tumour promotion and metastasis [J].

Bollrath, Julia ;

Greten, Florian R. .

EMBO REPORTS, 2009, 10 (12) :1314-1319

[4] Epigenetics of Aging and Aging-related Disease [J].

Brunet, Anne ;

Berger, Shelley L. .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2014, 69 :S17-S20

[5] Aging, Cellular Senescence, and Cancer [J].

Campisi, Judith .

ANNUAL REVIEW OF PHYSIOLOGY, VOL 75, 2013, 75 :685-705

[6] Bcl3 regulates pro-survival and pro-inflammatory gene expression in cutaneous T-cell lymphoma [J].

Chang, Tzu-Pei ;

Vancurova, Ivana .

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2014, 1843 (11) :2620-2630

[7] Broad H3K4me3 is associated with increased transcription elongation and enhancer activity at tumor-suppressor genes [J].

Chen, Kaifu ;

Chen, Zhong ;

Wu, Dayong ;

Zhang, Lili ;

Lin, Xueqiu ;

Su, Jianzhong ;

Rodriguez, Benjamin ;

Xi, Yuanxin ;

Xia, Zheng ;

Chen, Xi ;

Shi, Xiaobing ;

Wang, Qianben ;

Li, Wei .

NATURE GENETICS, 2015, 47 (10) :1149-+

[8] STAR: ultrafast universal RNA-seq aligner [J].

Dobin, Alexander ;

Davis, Carrie A. ;

Schlesinger, Felix ;

Drenkow, Jorg ;

Zaleski, Chris ;

Jha, Sonali ;

Batut, Philippe ;

Chaisson, Mark ;

Gingeras, Thomas R. .

BIOINFORMATICS, 2013, 29 (01) :15-21

[9]

Franceschi C, 2000, ANN NY ACAD SCI, V908, P244

[10] Chronic Inflammation (Inflammaging) and Its Potential Contribution to Age-Associated Diseases [J].

Franceschi, Claudio ;

Campisi, Judith .

JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES, 2014, 69 :S4-S9

← 1 2 3 4 →