Connecting homocysteine and obesity through pyroptosis, gut microbiome, epigenetics, peroxisome proliferator-activated receptor γ, and zinc finger protein 407

2018 ◽  
Vol 96 (10) ◽  
pp. 971-976 ◽  
Author(s):  
Anwesha Laha ◽  
Avisek Majumder ◽  
Mahavir Singh ◽  
Suresh C. Tyagi
Keyword(s):  
Zinc Finger ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Zinc Finger Protein ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Divalent Metal Ions ◽  
Peroxisome Proliferator Activated Receptor ◽  
Finger Protein

Although homocysteine (Hcy), a part of the epigenome, contributes to cell death by pyroptosis and decreases peroxisome proliferator-activated receptor γ (PPARγ) levels, the mechanisms are unclear. Hcy is found in high concentrations in the sera of obese individuals, which can elicit an immune response as well by hypermethylating CpG islands of specific gene promoters, a marker of epigenetics. Hcy has also been established to chelate divalent metal ions like Cu2+ and Zn2+, but this role of Hcy has not been established in relationship with obesity. It has been known for a while that PPARγ dysregulation results in various metabolic disorders including glucose and lipid metabolism. Recently, zinc finger protein 407 (Zfp407) is reported to regulate PPARγ target gene expression without affecting PPARγ transcript and protein levels by synergistically working with PPARγ. However, the mechanism(s) of this synergy, as well as other factors contributing to or inhibiting this synergism, have not been proven. This review suggests that Hcy contributes to pyroptosis, changes gut microbiome, and alters PPARγ-dependent mechanism(s) via Zfp407-mediated upregulated adipogenesis and misbalanced fatty acid metabolism, which can predispose to obesity and, consequently, obesity-related metabolic disorders.

Identification of a Novel Peroxisome Proliferator Responsive cDNA Isolated from Rat Hepatocytes as the Zinc-Finger Protein ZFP-37

1998 ◽  
Vol 152 (1) ◽  
pp. 107-118 ◽  
Author(s):  
John P. Vanden Heuvel ◽  
Peter Holden ◽  
Jonathan Tugwood ◽  
Christine Ingle ◽  
Weiyi Yen ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Rat Hepatocytes ◽  
Peroxisome Proliferator ◽  
Finger Protein

scholarly journals Activated Liver X Receptors Stimulate Adipocyte Differentiation through Induction of Peroxisome Proliferator-Activated Receptor γ Expression

2004 ◽  
Vol 24 (8) ◽  
pp. 3430-3444 ◽  
Author(s):  
Jong Bae Seo ◽  
Hyang Mi Moon ◽  
Woo Sik Kim ◽  
Yun Sok Lee ◽  
Hyun Woo Jeong ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Gene ◽  
Adipocyte Differentiation ◽  
Specific Gene ◽  
Peroxisome Proliferator ◽  
Liver X Receptors ◽  
Gene Promoters ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Gene Expression ◽  
X Receptors

ABSTRACT Liver X receptors (LXRs) are nuclear hormone receptors that regulate cholesterol and fatty acid metabolism in liver tissue and in macrophages. Although LXR activation enhances lipogenesis, it is not well understood whether LXRs are involved in adipocyte differentiation. Here, we show that LXR activation stimulated the execution of adipogenesis, as determined by lipid droplet accumulation and adipocyte-specific gene expression in vivo and in vitro. In adipocytes, LXR activation with T0901317 primarily enhanced the expression of lipogenic genes such as the ADD1/SREBP1c and FAS genes and substantially increased the expression of the adipocyte-specific genes encoding PPARγ (peroxisome proliferator-activated receptor γ) and aP2. Administration of the LXR agonist T0901317 to lean mice promoted the expression of most lipogenic and adipogenic genes in fat and liver tissues. It is of interest that the PPARγ gene is a novel target gene of LXR, since the PPARγ promoter contains the conserved binding site of LXR and was transactivated by the expression of LXRα. Moreover, activated LXRα exhibited an increase of DNA binding to its target gene promoters, such as ADD1/SREBP1c and PPARγ, which appeared to be closely associated with hyperacetylation of histone H3 in the promoter regions of those genes. Furthermore, the suppression of LXRα by small interfering RNA attenuated adipocyte differentiation. Taken together, these results suggest that LXR plays a role in the execution of adipocyte differentiation by regulation of lipogenesis and adipocyte-specific gene expression.

scholarly journals Control of Hepatic Gluconeogenesis by the Promyelocytic Leukemia Zinc Finger Protein

2014 ◽  
Vol 28 (12) ◽  
pp. 1987-1998 ◽  
Author(s):  
Siyu Chen ◽  
Jinchun Qian ◽  
Xiaoli Shi ◽  
Tingting Gao ◽  
Tingming Liang ◽  
...  
Keyword(s):  
Zinc Finger ◽  
Metabolic Diseases ◽  
Zinc Finger Protein ◽  
Promyelocytic Leukemia ◽  
Peroxisome Proliferator ◽  
Hepatic Gluconeogenesis ◽  
Promyelocytic Leukemia Zinc Finger ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hepatic Glucose ◽  
Glucose Output

The promyelocytic leukemia zinc finger (PLZF) protein is involved in major biological processes including energy metabolism, although its role remains unknown. In this study, we demonstrated that hepatic PLZF expression was induced in fasted or diabetic mice. PLZF promoted gluconeogenic gene expression and hepatic glucose output, leading to hyperglycemia. In contrast, hepatic PLZF knockdown improved glucose homeostasis in db/db mice. Mechanistically, peroxisome proliferator-activated receptor γ coactivator 1α and the glucocorticoid receptor synergistically activated PLZF expression. We conclude that PLZF is a critical regulator of hepatic gluconeogenesis. PLZF manipulation may benefit the treatment of metabolic diseases associated with gluconeogenesis.

scholarly journals Identification of Zfp393, a germ cell-specific gene encoding a novel zinc finger protein

2002 ◽  
Vol 118 (1-2) ◽  
pp. 233-239 ◽  
Author(s):  
Wei Yan ◽  
Kathleen H Burns ◽  
Lang Ma ◽  
Martin M Matzuk
Keyword(s):  
Germ Cell ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Specific Gene ◽  
Gene Encoding ◽  
Finger Protein

scholarly journals Drosophila Zinc Finger Protein CG9890 Is Colocalized with Chromatin Modifying and Remodeling Complexes on Gene Promoters and Involved in Transcription Regulation

Acta Naturae ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 114-119
Author(s):  
N. A. Fursova ◽  
M. Y. Mazina ◽  
J. V. Nikolenko ◽  
N. E. Vorobyova ◽  
A. N. Krasnov
Keyword(s):  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Gene Promoters ◽  
Replication Complex ◽  
Finger Protein ◽  
Genome Wide ◽  
A Genome ◽  
Nucleosome Density ◽  
Genome Wide Study ◽  
Transcription And Replication

In this work, we conducted a genome-wide study of the zinc finger protein CG9890 and showed that it is localized mostly on the promoters of active genes. The CG9890 binding sites are low-nucleosome-density regions and are colocalized with the chromatin modifying and remodeling complexes SAGA and dSWI/SNF, as well as with the ORC replication complex. The CG9890 protein was shown to be involved in the regulation of the expression of some genes on the promoters of which it is located, with the ecdysone cascade genes accounting for a significant percentage of these genes. Thus, the CG9890 protein is a new member of the transcriptional network which is localized on active promoters, interacts with the main transcription and replication complexes, and is involved in the regulation of both basal and inducible transcription.

scholarly journals Transcriptional Regulation of the CLC-K1 Promoter by myc-Associated Zinc Finger Protein and Kidney-Enriched Krüppel-Like Factor, a Novel Zinc Finger Repressor

2000 ◽  
Vol 20 (19) ◽  
pp. 7319-7331 ◽  
Author(s):  
Shinichi Uchida ◽  
Yujiro Tanaka ◽  
Hiroshi Ito ◽  
Fumiko Saitoh-Ohara ◽  
Johji Inazawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Mesangial Cells ◽  
Specific Binding ◽  
Consensus Sequence ◽  
Interstitial Cells ◽  
Luciferase Reporter ◽  
Gene Promoters ◽  
Finger Protein

ABSTRACT The expression of CLC-K1 and CLC-K2, two kidney-specific CLC chloride channels, is transcriptionally regulated on a tissue-specific basis. Previous studies have shown that a GA element near their transcriptional start sites is important for basal and cell-specific activities of the CLC-K1 and CLC-K2 gene promoters. To identify the GA-binding proteins, the human kidney cDNA library was screened by a yeast one-hybrid system. A novel member of the Cys2-His2 zinc finger gene designated KKLF (for “kidney-enriched Krüppel-like factor”) and the previously isolated MAZ (for “myc-associated zinc finger protein”) were cloned. KKLF was found to be abundantly expressed in the liver, kidneys, heart, and skeletal muscle, and immunohistochemistry revealed the nuclear localization of KKLF protein in interstitial cells in heart and skeletal muscle, stellate cells, and fibroblasts in the liver. In the kidneys, KKLF protein was localized in interstitial cells, mesangial cells, and nephron segments, where CLC-K1 and CLC-K2 were not expressed. A gel mobility shift assay revealed sequence-specific binding of recombinant KKLF and MAZ proteins to the CLC-K1 GA element, and the fine-mutation assay clarified that the consensus sequence for the KKLF binding site was GGGGNGGNG. In a transient-transfection experiment, MAZ had a strong activating effect on transcription of the CLC-K1–luciferase reporter gene. On the other hand, KKLF coexpression with MAZ appeared to block the activating effect of MAZ. These results suggest that a novel set of zinc finger proteins may help regulate the strict tissue- and nephron segment-specific expression of the CLC-K1 and CLC-K2 channel genes through their GA cis element.

scholarly journals ZNF536, a Novel Zinc Finger Protein Specifically Expressed in the Brain, Negatively Regulates Neuron Differentiation by Repressing Retinoic Acid-Induced Gene Transcription

2009 ◽  
Vol 29 (13) ◽  
pp. 3633-3643 ◽  
Author(s):  
Zhen Qin ◽  
Fangli Ren ◽  
Xialian Xu ◽  
Yongming Ren ◽  
Hongge Li ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Neuronal Differentiation ◽  
Zinc Finger ◽  
Zinc Finger Protein ◽  
Marker Genes ◽  
Specific Gene ◽  
Specific Marker ◽  
Neuron Differentiation ◽  
Finger Protein ◽  
The Brain

ABSTRACT Neuronal differentiation is tightly regulated by a variety of factors. In a search for neuron-specific genes, we identified a highly conserved novel zinc finger protein, ZNF536. We observed that ZNF536 is most abundant in the brain and, in particular, is expressed in the developing central nervous system and dorsal root ganglia and localized in the cerebral cortex, hippocampus, and hypothalamic area. During neuronal differentiation of P19 cells induced by retinoic acid (RA), ZNF536 expression is increased at an early stage, and it is maintained at a constant level in later stages. Overexpression of ZNF536 results in an inhibition of RA-induced neuronal differentiation, while depletion or mutation of the ZNF536 gene results in an enhancement of differentiation. We further demonstrated that ZNF536 inhibits expression of neuron-specific marker genes, possibly through the inhibition of RA response element-mediated transcriptional activity, as overexpression of RA receptor α can rescue the inhibitory role of ZNF536 in neuronal differentiation and neuron-specific gene expression. Our studies have identified a novel zinc finger protein that negatively regulates neuron differentiation.

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