Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway

Chunyu Jin; Jing Li; Christopher D. Green; Xiaoming Yu; Xia Tang; Dali Han; Bo Xian; Dan Wang; Xinxin Huang; Xiongwen Cao; Zheng Yan; Lei Hou; Jiancheng Liu; Nicholas Shukeir; Philipp Khaitovich; Charlie D. Chen; Hong Zhang; Thomas Jenuwein; Jing Dong J. Han

doi:10.1016/j.cmet.2011.07.001

Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway

Chunyu Jin
, Jing Li
, Christopher D. Green
, Xiaoming Yu
, Xia Tang
, Dali Han
, Bo Xian
, Dan Wang
, Xinxin Huang
, Xiongwen Cao
, Zheng Yan
, Lei Hou
, Jiancheng Liu
, Nicholas Shukeir
, Philipp Khaitovich
, Charlie D. Chen
, Hong Zhang
, Thomas Jenuwein
, Jing Dong J. Han^*

^*Corresponding author for this work

CAS - Shanghai Institute of Nutrition and Health
CAS - Institute of Genetics and Developmental Biology
University of Chinese Academy of Sciences
National Institute of Biological Sciences, Beijing
CAS - Center for Excellence in Molecular Cell Science
Max Planck Institute of Immunobiology and Epigenetics
Max Planck Institute for Evolutionary Anthropology

Research output: Contribution to journal › Article › peer-review

217 Scopus citations

Abstract

Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ∼30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

Original language	English
Pages (from-to)	161-172
Number of pages	12
Journal	Cell Metabolism
Volume	14
Issue number	2
DOIs	https://doi.org/10.1016/j.cmet.2011.07.001
State	Published - 3 Aug 2011
Externally published	Yes

Access to Document

10.1016/j.cmet.2011.07.001

Cite this

Jin, C., Li, J., Green, C. D., Yu, X., Tang, X., Han, D., Xian, B., Wang, D., Huang, X., Cao, X., Yan, Z., Hou, L., Liu, J., Shukeir, N., Khaitovich, P., Chen, C. D., Zhang, H., Jenuwein, T., & Han, J. D. J. (2011). Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway. Cell Metabolism, 14(2), 161-172. https://doi.org/10.1016/j.cmet.2011.07.001

@article{eac2474535ec4bf2b21ba2214d0f60f3,

title = "Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway",

abstract = "Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ∼30\%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more {"}naive{"} epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help {"}reset{"} the developmental age of animal cells.",

author = "Chunyu Jin and Jing Li and Green, \{Christopher D.\} and Xiaoming Yu and Xia Tang and Dali Han and Bo Xian and Dan Wang and Xinxin Huang and Xiongwen Cao and Zheng Yan and Lei Hou and Jiancheng Liu and Nicholas Shukeir and Philipp Khaitovich and Chen, \{Charlie D.\} and Hong Zhang and Thomas Jenuwein and Han, \{Jing Dong J.\}",

year = "2011",

month = aug,

day = "3",

doi = "10.1016/j.cmet.2011.07.001",

language = "英语",

volume = "14",

pages = "161--172",

journal = "Cell Metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "2",

}

Jin, C, Li, J, Green, CD, Yu, X, Tang, X, Han, D, Xian, B, Wang, D, Huang, X, Cao, X, Yan, Z, Hou, L, Liu, J, Shukeir, N, Khaitovich, P, Chen, CD, Zhang, H, Jenuwein, T & Han, JDJ 2011, 'Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway', Cell Metabolism, vol. 14, no. 2, pp. 161-172. https://doi.org/10.1016/j.cmet.2011.07.001

TY - JOUR

T1 - Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway

AU - Jin, Chunyu

AU - Li, Jing

AU - Green, Christopher D.

AU - Yu, Xiaoming

AU - Tang, Xia

AU - Han, Dali

AU - Xian, Bo

AU - Wang, Dan

AU - Huang, Xinxin

AU - Cao, Xiongwen

AU - Yan, Zheng

AU - Hou, Lei

AU - Liu, Jiancheng

AU - Shukeir, Nicholas

AU - Khaitovich, Philipp

AU - Chen, Charlie D.

AU - Zhang, Hong

AU - Jenuwein, Thomas

AU - Han, Jing Dong J.

PY - 2011/8/3

Y1 - 2011/8/3

N2 - Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ∼30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

AB - Epigenetic modifications are thought to be important for gene expression changes during development and aging. However, besides the Sir2 histone deacetylase in somatic tissues and H3K4 trimethylation in germlines, there is scant evidence implicating epigenetic regulations in aging. The insulin/IGF-1 signaling (IIS) pathway is a major life span regulatory pathway. Here, we show that progressive increases in gene expression and loss of H3K27me3 on IIS components are due, at least in part, to increased activity of the H3K27 demethylase UTX-1 during aging. RNAi of the utx-1 gene extended the mean life span of C. elegans by ∼30%, dependent on DAF-16 activity and not additive in daf-2 mutants. The loss of utx-1 increased H3K27me3 on the Igf1r/daf-2 gene and decreased IIS activity, leading to a more "naive" epigenetic state. Like stem cell reprogramming, our results suggest that reestablishment of epigenetic marks lost during aging might help "reset" the developmental age of animal cells.

UR - https://www.scopus.com/pages/publications/79960936857

U2 - 10.1016/j.cmet.2011.07.001

DO - 10.1016/j.cmet.2011.07.001

M3 - 文章

C2 - 21803287

AN - SCOPUS:79960936857

SN - 1550-4131

VL - 14

SP - 161

EP - 172

JO - Cell Metabolism

JF - Cell Metabolism

IS - 2

ER -

Histone demethylase UTX-1 regulates C. elegans life span by targeting the insulin/IGF-1 signaling pathway

Abstract

Access to Document

Other files and links

Fingerprint

Cite this