B-cell translocation gene 2 promotes hepatic hepcidin production via induction of Yin Yang 1

Lee, Sung‐Eun; Hwang, Soo Min; Jang, Won‐Gu; Chang, Hyeun Wook; Kim, Yong Deuk

doi:10.1016/j.bbrc.2015.03.140

Cited by 8 publications

(32 citation statements)

References 18 publications

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“…82 BTG2 is predominantly expressed in a variety of tissues, including liver, and it is increased by various stress conditions; on the other hand, it is attenuated by insulin, estrogen, and growth factors. 82,83 Lee et al 84 revealed that BTG2 elevates hepcidin production by promoting YY1 expression, indicating a regulatory role for BTG2 on YY1 expression. Recently, a member of that same research group reported the markedly elevated levels of bile acid and the expression of CB1R and BTG2, together with the significantly increased expression of YY1 and bile acid synthetic enzymes in the liver tissue of an ALD mouse model.…”

Section: Yy1 and Dysregulated Bile Acid Metabolismmentioning

confidence: 99%

Multifunctional YY1 in Liver Diseases

Zhang

Yang

et al. 2017

Semin Liver Dis

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The transcription factor Yin Yang 1 (YY1) is a multifunctional protein that can activate or repress gene expression, depending on the cellular context. While YY1 is ubiquitously expressed and highly conserved between species, its role varies among the diverse cell types and includes proliferation, differentiation, and apoptosis. Upregulated YY1 expression is found in pathogenic conditions, such as human hepatocellular carcinoma and hepatitis B virus infection, and its roles in the molecular pathogenic mechanisms in liver (i.e., fibrosis, carcinogenesis, viral-induced injury) are currently being elucidated. The most recent studies have revealed that YY1 is deeply involved in such dysregulated cellular metabolisms as glycometabolism, lipid metabolism, and bile acid metabolism, which are all involved in various diseases. In this review, we will summarize the current knowledge on YY1 in liver diseases, providing a focused discussion on the characterized and probable underlying mechanisms, as well as a reasoned evaluation of the potential for YY1-mediated pathology as drug targets in liver disease therapies.

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Section: Yy1 and Dysregulated Bile Acid Metabolismmentioning

confidence: 99%

Multifunctional YY1 in Liver Diseases

Zhang

Yang

et al. 2017

Semin Liver Dis

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“…Proteins were extracted from liver tissues and analyzed using a Western blot analysis according to previously described methods . Membranes were probed with antibodies against BTG2, YY1, CYP7A1, and β‐actin (SantaCruz Biotechnology, Santa Cruz, CA, USA) and then detected using an ECL Western blot detection kit (Amersham Bioscience, Piscataway, NJ, USA).…”

Section: Methodsmentioning

confidence: 99%

“…The reporter gene for mouse Cyp7a1 and expression vectors of Btg2 and Yy1 have been described previously . A point mutant form of m Cyp7a1 ‐Luc was generated using the QuikChange II Site‐Directed Mutagenesis kit (Stratagene, La Jolla, CA, USA), and the constructs were confirmed by DNA sequencing, as described previously .…”

Section: Methodsmentioning

confidence: 99%

“…BTG2 is increased by hypoxia, oxidative stress, metabolic changes, and retinoic acid, while it is attenuated by insulin, estrogen, and growth factors . Notably, we have revealed that BTG2, a transcriptional co‐regulator, elevates hepcidin production by promoting Yin Ying 1 (YY1) . YY1, a zinc‐finger transcription factor, belongs to the Polycomb group protein family and acts as a transcriptional activator and repressor by binding to consensus sequences (CCATNTT).…”

Section: Introductionmentioning

confidence: 99%

“…YY1, a zinc‐finger transcription factor, belongs to the Polycomb group protein family and acts as a transcriptional activator and repressor by binding to consensus sequences (CCATNTT). It is highly expressed in various tissues and associated with biological conditions, including proliferation, differentiation, apoptosis, development, and replication . Indeed, YY1 also regulates the transcription of target genes involved in diverse pathophysiological processes, including gluconeogenesis, steatosis, and cancer .…”

Section: Introductionmentioning

confidence: 99%

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Melatonin ameliorates alcohol‐induced bile acid synthesis by enhancing miR‐497 expression

Kim

Hwang

Kim

et al. 2017

Journal of Pineal Research

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Alcoholic liver disease is a major cause of chronic liver disease worldwide, and cannabinoid receptor type 1 (CB1R) is involved in a diverse metabolic diseases. B-cell translocation gene 2 (BTG2) and yin yang 1 (YY1) are a potent regulator of biological conditions. Melatonin plays a crucial role in regulating diverse physiological functions and metabolic homeostasis. MicroRNAs are key regulators of various biological processes. Herein, we demonstrate that melatonin improves bile acid synthesis in the liver of alcohol-fed mice by controlling miR-497 expression. The level of bile acid and the expression of Cb1r, Btg2, Yy1, and bile acid synthetic enzymes were significantly elevated in the livers of Lieber-DeCarli alcohol-fed mice. The overexpression of Btg2 enhanced Yy1 gene expression and bile acid production, whereas disrupting the CB1R-BTG2-YY1 cascade protected against the bile acid synthesis caused by alcohol challenge. We identified an alcohol-mediated YY1 binding site on the cholesterol 7α-hydroxylase (Cyp7a1) gene promoter using promoter deletion analysis and chromatin immunoprecipitation assays. Notably, melatonin attenuated the alcohol-stimulated induction of Btg2, Yy1 mRNA levels and bile acid production by promoting miR-497. Overexpression of a miR-497 mimic dramatically diminished the increase of Btg2 and Yy1 gene expression as well as bile acid production by alcohol, whereas this phenomenon was reversed by miR-497 inhibitor. These results demonstrate that the upregulation of miR-497 by melatonin represses alcoholinduced bile acid synthesis by attenuating the BTG2-YY1 signaling pathway. The melatonin-miR497 signaling network may provide novel therapeutic targets for the treatment of hepatic metabolic dysfunction caused by the alcohol-dependent pathway.

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Advances in understanding the regulatory mechanism of cholesterol 7α-hydroxylase

Shao

2019

Biochemical Pharmacology

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B-cell translocation gene 2 promotes hepatic hepcidin production via induction of Yin Yang 1

Cited by 8 publications

References 18 publications

Multifunctional YY1 in Liver Diseases

Multifunctional YY1 in Liver Diseases

Melatonin ameliorates alcohol‐induced bile acid synthesis by enhancing miR‐497 expression

Advances in understanding the regulatory mechanism of cholesterol 7α-hydroxylase

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