Metabolomics Reveals a Role for the Chromatin-Binding Protein HMGN5 in Glutathione Metabolism

被引：9

作者：

Ciappio, Eric D. ^{[1
]}

Krausz, Kristopher W. ^{[1
]}

Rochman, Mark ^{[1
]}

Furusawa, Takashi ^{[1
]}

Bonzo, Jessica A. ^{[1
]}

Tessarollo, Lino ^{[2
]}

Gonzalez, Frank J. ^{[1
]}

Bustin, Michael ^{[1
]}

机构：

[1] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA

[2] NCI, Neural Dev Sect, Mouse Canc Genet Program, Frederick, MD 21701 USA

来源：

PLOS ONE | 2014年 / 9卷 / 01期

基金：

美国国家卫生研究院; 美国国家科学基金会;

关键词：

GAMMA-GLUTAMYLCYSTEINE SYNTHETASE; HISTONE H1; FAMILY; METLIN;

D O I：

10.1371/journal.pone.0084583

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：

High mobility group nucleosome-binding protein 5 (HMGN5) is a chromatin architectural protein that binds specifically to nucleosomes and reduces the compaction of the chromatin fiber. The protein is present in most vertebrate tissues however the physiological function of this protein is unknown. To examine the function of HMGN5 in vivo, mice lacking the nucleosome-binding domain of HMGN5 were generated and characterized. Serological analysis revealed that compared to wild-type littermates (Hmgn5(+/Y)), mice with a targeted mutation in the HMGN5 gene (Hmgn5(tm1/Y)), had elevated serum albumin, non-HDL cholesterol, triglycerides, and alanine transaminase, suggesting mild hepatic abnormalities. Metabolomics analysis of liver extracts and urine revealed clear differences in metabolites between Hmgn5(tm1/Y) and their Hmgn5(+/Y) littermates. Hmgn5(tm1/Y) mice had a significant increase in hepatic glutathione levels and decreased urinary concentrations of betaine, phenylacetylglycine, and creatine, all of which are metabolically related to the glutathione precursor glycine. Microarray and qPCR analysis revealed that expression of two genes affecting glutathione metabolism, glutathione peroxidase 6 (Gpx6) and hexokinase 1 (Hk1), was significantly decreased in Hmgn5(tm1/Y) mouse liver tissue. Analysis of chromatin structure by DNase I digestion revealed alterations in the chromatin structure of these genes in the livers of Hmgn5(tm1/Y) mice. Thus, functional loss of HMGN5 leads to changes in transcription of Gpx6 and Hk1 that alter glutathione metabolism.

引用

页数：10

共 32 条

[1] The Chromatin-binding Protein HMGN1 Regulates the Expression of Methyl CpG-binding Protein 2 (MECP2) and Affects the Behavior of Mice [J].