The histone methyltransferase Suv39h2 contributes to nonalcoholic steatohepatitis in mice

Fan, Zhiwen; Li, Luyang; Li, Min; Zhang, Xinjian; Hao, Chenzhi; Yu, Liming; Zeng, Sheng; Xu, Huihui; Fang, Mingming; Shen, Aiguo; Jenuwein, Thomas; Xu, Yong

doi:10.1002/hep.29127

Cited by 51 publications

(32 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previously we have shown that SIRT1 expression is epigenetically regulated in different disease settings. For instance, nutritional stress-induced down-regulation of SIRT1 in both hepatocytes and macrophages appears to be mediated by the histone trimethyltransferase Suv39h2 (42). Similarly, SIRT1 transrepression in cardiomyocytes in response to ischemic stress relies on the histone trimethyltransferase Suv39h1 (43).…”

Section: Discussionmentioning

confidence: 99%

SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice

Hong

Hao

et al. 2017

FASEB j.

Self Cite

View full text Add to dashboard Cite

Hepatic stellate cells (HSCs) are a major source of fibrogenesis in the liver, contributing to cirrhosis. When activated, HSCs transdifferentiate into myofibroblasts and undergo profound functional alterations paralleling an overhaul of the transcriptome, the mechanism of which remains largely undefined. We investigated the involvement of the class III deacetylase sirtuin [silent information regulator 1 (SIRT1)] in HSC activation and liver fibrosis. SIRT1 levels were down-regulated in the livers in mouse models of liver fibrosis, in patients with cirrhosis, and in activated HSCs as opposed to quiescent HSCs. SIRT1 activation halted, whereas SIRT1 inhibition promoted, HSC transdifferentiation into myofibroblasts. Liver fibrosis was exacerbated in mice with HSC-specific deletion of SIRT1 [conditional knockout (cKO)], receiving CCl (1 mg/kg) injection or subjected to bile duct ligation, compared to wild-type littermates. SIRT1 regulated peroxisome proliferator activated receptor γ (PPARγ) transcription by deacetylating enhancer of zeste homolog 2 (EZH2) in quiescent HSCs. Finally, EZH2 inhibition or PPARγ activation ameliorated fibrogenesis in cKO mice. In summary, our data suggest that SIRT1 plays an essential role guiding the transition of HSC phenotypes.-Li, M., Hong, W., Hao, C., Li, L., Wu, D., Shen, A., Lu, J., Zheng, Y., Li, P., Xu, Y. SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice.

show abstract

Section: Discussionmentioning

confidence: 99%

SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice

Hong

Hao

et al. 2017

FASEB j.

Self Cite

View full text Add to dashboard Cite

show abstract

“…Primary mouse hepatocytes were isolated and maintained as previously described by Fan et al (15). The Wnt3a-producing (CRL2647; American Type Culture Collection, Manassas, VA, USA) were maintained as previously described by Soeda et al (16).…”

Section: Cell Culture and Transient Transfectionmentioning

confidence: 99%

Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/β‐catenin pathway in mice

Kong

Zeng

et al. 2018

The FASEB Journal

Self Cite

View full text Add to dashboard Cite

Liver regeneration is a complicated pathophysiologic process that is regulated by a myriad of signaling pathways and transcription factors. The interaction among these pathways and factors, either cooperatively or antagonistically, may ultimately lead to recovery and restoration of liver function or permanent loss of liver function and liver failure. In the present study, we investigated the mechanism whereby the chromatin remodeling protein brahma related gene 1 (Brg1) regulates liver regeneration in mice. The Smarca4-Flox strain of mice was crossbred with the Alb-Cre strain to generate hepatocyte-specific Brg1 knockout mice. Liver injury was induced by partial hepatectomy (PHx). We report that Brg1 deletion in hepatocyte compromised liver regeneration and dampened survival after PHx in mice. Brg1 interacted with β-catenin to potentiate Wnt signaling and promote hepatocyte proliferation. Mechanistically, Brg1 recruited lysine demethylase 4 (KDM4) to activate β-catenin target genes. Our data suggest that Brg1 might play an essential role maintaining hepatic homeostasis and contributing to liver repair.-Li, N., Kong, M., Zeng, S., Hao, C., Li, M., Li, L., Xu, Z., Zhu, M., Xu, Y. Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/β-catenin pathway in mice.

show abstract

“…Increasing evidence has confirmed that dysregulation of SUV39H2 contributes to carcinogenesis and is involved in invasion and metastasis of malignancy [33,36,38,41,42,44]. Recently, researches have also clarified that Suv39h2 knockout decrease the incidence of nonalcoholic steatohepatitis and myocardial infarction [48][49][50]. In this review, we focus on the prognostic value of SUV39H2 in cancers, describe the off-target effects of SUV39H2 on non-histone proteins in epigenetic modification, discuss its potential mechanisms in tumorigenesis and immunotherapy, and, summarize SUV39H2 inhibition as a potential target for anti-cancer therapies ( Table 1).…”

Section: Breast Cancermentioning

confidence: 98%

“…The mRNA and protein expression levels of SUV39H2, G9a and EZH2 are up-regulated in hepatocellular carcinoma (HCC) tissues and SUV39H2 is highly associated with the HCV infection and tumor stage [43]. In hepatocytes, Suv39H2 increases the incidence of nonalcoholic steatohepatitis and steatosis likely via increasing H3K9me3 on Sirt1 gene promoter and promoting SIRT1 trans-repression in mice [48,50]. These all imply a potential role of SUV39H2 in HCC pathogenesis and progression.…”

Section: Hepatocellular Carcinomamentioning

confidence: 99%

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

Li¹,

Zheng²,

Yang³

2019

J. Cancer

View full text Add to dashboard Cite

Epigenetic modifications at the histone level have attracted significant attention because of their roles in tumorigenesis. Suppressor of variegation 3-9 homolog 2 (SUV39H2, also known as KMT1B) is a member of the SUV39 subfamily of lysine methyltransferases (KMTs) that plays a significant role in histone H3-K9 di-/tri-methylation, transcriptional regulation and cell cycle. Overexpressions of SUV39H2 at gene, mRNA and protein levels are known to be associated with a range of cancers: leukemia, lymphomas, lung cancer, breast cancer, colorectal cancer, gastric cancer, hepatocellular cancer and so on. Accumulating evidence indicates that SUV39H2 acts as an oncogene and contributes to the initiation and progression of cancers. It could, therefore, be a promising target for anti-cancer treatment. In this review, we focus on the dysregulation of SUV39H2 in cancers, including its clinical prognostic predictor role, molecular mechanism involved in cancer occurrence and development, relevant inhibitors against cancer, and its epigenetic modification interaction with immunotherapy. A better understanding of the SUV39H2 will be beneficial to the development of molecular-targeted therapies in cancer.

show abstract

The histone methyltransferase Suv39h2 contributes to nonalcoholic steatohepatitis in mice

Abstract: Suv39h2 plays a pivotal role in the regulation of inflammatory response in hepatocytes and macrophages, contributing to NASH pathogenesis. (Hepatology 2017;65:1904-1919).

Cited by 51 publications

References 50 publications

SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice

SIRT1 antagonizes liver fibrosis by blocking hepatic stellate cell activation in mice

Brahma related gene 1 (Brg1) contributes to liver regeneration by epigenetically activating the Wnt/β‐catenin pathway in mice

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

Contact Info

Product

Resources

About