Regulation of Melanophilin (Mlph) gene expression by the glucocorticoid receptor (GR)

AbstractMlph plays a crucial role in regulating skin pigmentation through the melanosome transport process. Although Mlph is a major component involved in melanosome transport, the mechanism that regulates the expression of the Mlph gene has not been identified. In this study, we demonstrate that Mlph expression is regulated by the glucocorticoid receptor (GR). Alteration of GR activity using a specific GR agonist or antagonist only regulated the expression of Mlph among the 3 key melanosome transport proteins. Translocation of GR from the cytosol into the nucleus following Dex treatment was confirmed by separating the cytosol and nuclear fractions and by immunofluorescence staining. In ChIP assays, Dex induced GR binding to the Mlph promoter and we determined that Dex induced the GR binding motif on the Mlph promoter. Our findings contribute to understanding the regulation of Mlph expression and to the novel role of GR in Mlph gene expression.

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Haunted Chinese Gay Identity

The Cosmopolitan Dream ◽

10.5790/hongkong/9789888455850.003.0005 ◽

2018 ◽

pp. 73-86

Author(s):

Hongwei Bao

Keyword(s):

Crucial Role ◽

Gay Identity ◽

The Novel ◽

Social Critique ◽

Subject Formation ◽

Contemporary China ◽

Potential Productivity ◽

Chinese Context ◽

Historical Memories

This chapter examines the construction of Chinese gay identity in a popular queer online fiction titled Beijing Story. Drawing on the Derridian notion of “hauntology”, I propose to read the novel as a social critique of postsocialist China in the context of globalization and neoliberalism. I highlight the intersections between sexuality, masculinity, and class in the narrative, and the potential productivity of paying more attention to the issue of class in queer subject formation in contemporary China. I also emphasize the crucial role of the transnational, as well as historical forms of homoeroticism and recent historical memories of revolution and reconstruction, in constructing contemporary gay identity in China. In doing so, I critically assess the role of “queer Marxism” (Liu 2015) in a transnational Chinese context.

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The role of glucocorticoid receptor and gene expression in the anti-inflammatory action of dexamethasone

Nature ◽

10.1038/280408a0 ◽

1979 ◽

Vol 280 (5721) ◽

pp. 408-410 ◽

Cited By ~ 159

Author(s):

SUSUMU TSURUFUJI ◽

KAZUO SUGIO ◽

FUMIHIKO TAKEMASA

Keyword(s):

Gene Expression ◽

Glucocorticoid Receptor ◽

Anti Inflammatory ◽

Inflammatory Action

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The zinc-binding motif of human RECQ5β suppresses the intrinsic strand-annealing activity of its DExH helicase domain and is essential for the helicase activity of the enzyme

Biochemical Journal ◽

10.1042/bj20071150 ◽

2008 ◽

Vol 412 (3) ◽

pp. 425-433 ◽

Cited By ~ 23

Author(s):

Hua Ren ◽

Shuo-Xing Dou ◽

Xing-Dong Zhang ◽

Peng-Ye Wang ◽

Radhakrishnan Kanagaraj ◽

...

Keyword(s):

Structural Similarity ◽

Zinc Binding ◽

Binding Motif ◽

Dna Unwinding ◽

Helicase Domain ◽

The Novel ◽

Quantitative Measurements ◽

Strand Annealing ◽

Zinc Binding Motif

RecQ family helicases, functioning as caretakers of genomic integrity, contain a zinc-binding motif which is highly conserved among these helicases, but does not have a substantial structural similarity with any other known zinc-finger folds. In the present study, we show that a truncated variant of the human RECQ5β helicase comprised of the conserved helicase domain only, a splice variant named RECQ5α, possesses neither ATPase nor DNA-unwinding activities, but surprisingly displays a strong strand-annealing activity. In contrast, fragments of RECQ5β including the intact zinc-binding motif, which is located immediately downstream of the helicase domain, exhibit much reduced strand-annealing activity but are proficient in DNA unwinding. Quantitative measurements indicate that the regulatory role of the zinc-binding motif is achieved by enhancing the DNA-binding affinity of the enzyme. The novel intramolecular modulation of RECQ5β catalytic activity mediated by the zinc-binding motif may represent a universal regulation mode for all RecQ family helicases.

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Gene expression profiling identifies the novel role of immunoproteasome in doxorubicin-induced cardiotoxicity

Toxicology ◽

10.1016/j.tox.2015.04.009 ◽

2015 ◽

Vol 333 ◽

pp. 76-88 ◽

Cited By ~ 7

Author(s):

Wen-Jie Zhao ◽

Sheng-Nan Wei ◽

Xiang-Jun Zeng ◽

Yun-Long Xia ◽

Jie Du ◽

...

Keyword(s):

Gene Expression ◽

Gene Expression Profiling ◽

Expression Profiling ◽

The Novel

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The TAZ2 domain of CBP/p300 directs acetylation towards H3K27 within chromatin

10.1101/2020.07.21.214338 ◽

2020 ◽

Author(s):

Thomas W. Sheahan ◽

Viktoria Major ◽

Kimberly M. Webb ◽

Elana Bryan ◽

Philipp Voigt

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Enzymatic Activity ◽

Crucial Role ◽

Regulation Of Gene Expression ◽

Histone H3 ◽

Embryonic Stem ◽

Site Specific ◽

Lysine Residues

AbstractThe closely related acetyltransferases CBP and p300 are key regulators of gene expression in metazoans. CBP/p300 acetylate several specific lysine residues within nucleosomes, including histone H3 lysine 27 (H3K27), a hallmark of active enhancers and promoters. However, it has remained largely unclear how specificity of CBP/p300 towards H3K27 is achieved. Here we show that the TAZ2 domain of CBP is required for efficient acetylation of H3K27, while curbing activity towards other lysine residues within nucleosomes. We find that TAZ2 is a sequence-independent DNA binding module, promoting interaction between CBP and nucleosomes, thereby enhancing enzymatic activity and regulating substrate specificity of CBP. TAZ2 is further required to stabilize CBP binding to chromatin in mouse embryonic stem cells, facilitating specificity towards H3K27 and modulating gene expression. These findings reveal a crucial role of TAZ2 in regulating H3K27ac, while highlighting the importance of correct site-specific acetylation for proper regulation of gene expression.

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TAZ inhibits glucocorticoid receptor and coordinates hepatic glucose homeostasis in normal physiologic states

eLife ◽

10.7554/elife.57462 ◽

2021 ◽

Vol 10 ◽

Author(s):

Simiao Xu ◽

Yangyang Liu ◽

Ruixiang Hu ◽

Min Wang ◽

Oliver Stöhr ◽

...

Keyword(s):

Blood Glucose ◽

Glucocorticoid Receptor ◽

Glucose Homeostasis ◽

Mouse Liver ◽

Blood Glucose Concentration ◽

Glucose Production ◽

Binding Motif ◽

Gene Promoters ◽

Hepatic Glucose

The elucidation of the mechanisms whereby the liver maintains glucose homeostasis is crucial for the understanding of physiologic and pathologic states. Here, we show a novel role of hepatic transcriptional co-activator with PDZ-binding motif (TAZ) in the inhibition of glucocorticoid receptor (GR). TAZ is abundantly expressed in pericentral hepatocytes and its expression is markedly reduced by fasting. TAZ interacts via its WW domain with the ligand-binding domain of GR to limit the binding of GR to the GR response element in gluconeogenic gene promoters. Therefore, liver-specific TAZ knockout mice show increases in glucose production and blood glucose concentration. Conversely, the overexpression of TAZ in mouse liver reduces the binding of GR to gluconeogenic gene promoters and glucose production. Thus, our findings demonstrate that hepatic TAZ inhibits GR-transactivation of gluconeogenic genes and coordinates gluconeogenesis in response to physiologic fasting and feeding.

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