Zbtb7c is a critical gluconeogenic transcription factor that induces glucose-6-phosphatase and phosphoenylpyruvate carboxykinase 1 genes expression during mice fasting

Choi, Won‐Il; Yoon, John C.; Song, Jiwoon; Jeon, Bu‐Nam; Park, Joo-Man; Koh, Dong-In; Ahn, Yong-Ho; Kim, Kyung‐Sup; Lee, Inkyu; Hur, Man‐Wook

doi:10.1016/j.bbagrm.2019.04.001

Cited by 14 publications

(12 citation statements)

References 39 publications

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“…Recently, a study by Blue et al identified variants associated with age at onset of AD in ZBTB4, another gene from the same gene family, located on chromosome 17 41 . In addition, knock out of ZBTB7C in mice led to decreased glucose blood levels 42 . Moreover, this same study showed that Zbtb7c deacetylated forkhead box O1 (Foxo1), leading to increased Foxo1 binding and transcriptional activation of genes involved with glucogenesis.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Prokopenko

Hecker

Kirchner

et al. 2020

Sci Rep

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With the advent of whole genome-sequencing (WGS) studies, family-based designs enable sex-specific analysis approaches that can be applied to only affected individuals; tests using family-based designs are attractive because they are completely robust against the effects of population substructure. These advantages make family-based association tests (FBATs) that use siblings as well as parents especially suited for the analysis of late-onset diseases such as Alzheimer's Disease (AD). However, the application of FBATs to assess sex-specific effects can require additional filtering steps, as sensitivity to sequencing errors is amplified in this type of analysis. Here, we illustrate the implementation of robust analysis approaches and additional filtering steps that can minimize the chances of false positive-findings due to sex-specific sequencing errors. We apply this approach to two family-based AD datasets and identify four novel loci (GRID1, RIOK3, MCPH1, ZBTB7C) showing sex-specific association with AD risk. Following stringent quality control filtering, the strongest candidate is ZBTB7C (P inter = 1.83 × 10 −7 ), in which the minor allele of rs1944572 confers increased risk for AD in females and protection in males. ZBTB7C encodes the Zinc Finger and BTB Domain Containing 7C, a transcriptional repressor of membrane metalloproteases (MMP). Members of this MMP family were implicated in AD neuropathology.Alzheimer's disease (AD) is the most common form of dementia worldwide, with a substantial burden for not only patients, but their families, society and the healthcare system. The impact of the disease is expected to increase further by 2050, with a projected 13.9 million Americans to develop AD or related dementias 1 . Like most complex diseases, AD is caused by a mixture of genetic and environmental factors. Early-onset familial AD (monogenic) is caused by rare fully penetrant mutations in APP, PSEN1, PSEN2 genes 2 . The more prevalent form, late-onset (sporadic) AD, is caused by a complex polygenic architecture, including large-effect variants in the APOE gene 3 . Environmental and lifestyle factors also affect the prevalence of the disease, however this domain is less well elucidated to date. Although one of the strongest predictors for AD is age, there are several other risk factors, including race 4 , high blood pressure 5 , brain trauma 6 and sex 7-10 .Not only are women at twofold greater risk than men, the progression of the disease and neurodegeneration is more rapid among women versus men 11,12 . In contrast, men with AD have higher mortality, as compared to women 12,13 . Interactions between sex and APOE ε4 have been previously reported. For instance, Altmann et al. showed that women have greater AD risk in the presence of APOE ε4, and this APOE-related risk in women may

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Section: Discussionmentioning

confidence: 99%

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Prokopenko

Hecker

Kirchner

et al. 2020

Sci Rep

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“…to fasting, FOXO1 is deacetylated and thus activated by zinc finger and BTB domain-containing 7c (ZBTB7C) and SIRT1, as well as by histone deacetylases (HDACs) that are phosphorylated by AMPK (Frescas et al 2005;Mihaylova et al 2011;Choi et al 2019).…”

Section: Glucose Metabolismmentioning

confidence: 99%

Hepatic transcriptional responses to fasting and feeding

2021

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Mammals undergo regular cycles of fasting and feeding that engage dynamic transcriptional responses in metabolic tissues. Here we review advances in our understanding of the gene regulatory networks that contribute to hepatic responses to fasting and feeding. The advent of sequencing and -omics techniques have begun to facilitate a holistic understanding of the transcriptional landscape and its plasticity. We highlight transcription factors, their cofactors, and the pathways that they impact. We also discuss physiological factors that impinge on these responses, including circadian rhythms and sex differences. Finally, we review how dietary modifications modulate hepatic gene expression programs.

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“…All plasmid constructs were verified by DNA sequencing. Descriptions of the recombinant adenovirus shRNA and siRNA against Zbtb7c mRNA have been reported elsewhere 18 , 21 . Antibodies against p53, p300, SIRT1, AMPK, phosphorylated APMK, PGC-1, PPARγ, Zbtb7c, acetylated lysine, GAPDH, FLAG-Tag, Myc-Tag, Ac-H3, Ac-H4, and mSin3A were purchased from Upstate (Charlottesville, VA), Chemicon (Temecula, CA), Cell Signaling Technology (Beverly, MA), Calbiochem (San Diego, CA), and Santa Cruz Biotech (Santa Cruz, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Zbtb7c increases Fasn transcription 20 . Recently, we showed that Zbtb7c is vital in gluconeogenesis during fasting and in glutamine metabolism in cancer cells 21 , 22 . These results suggested that Zbtb7c might be an essential regulator of metabolism.…”

Section: Introductionmentioning

confidence: 99%

Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

et al. 2021

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Zbtb7c is a proto-oncoprotein that controls the cell cycle and glucose, glutamate, and lipid metabolism. Zbtb7c expression is increased in the liver and white adipose tissues of aging or high-fat diet-fed mice. Knockout or knockdown of Zbtb7c gene expression inhibits the adipocyte differentiation of 3T3-L1 cells and decreases adipose tissue mass in aging mice. We found that Zbtb7c was a potent transcriptional repressor of SIRT1 and that SIRT1 was derepressed in various tissues of Zbtb7c-KO mice. Mechanistically, Zbtb7c interacted with p53 and bound to the proximal promoter p53RE1 and p53RE2 to repress the SIRT1 gene, in which p53RE2 was particularly critical. Zbtb7c induced p53 to interact with the corepressor mSin3A-HADC1 complex at p53RE. By repressing the SIRT1 gene, Zbtb7c increased the acetylation of Pgc-1α and Pparγ, which resulted in repression or activation of Pgc-1α or Pparγ target genes involved in lipid metabolism. Our study provides a molecular target that can overexpress SIRT1 protein in the liver, pancreas, and adipose tissues, which can be beneficial in the treatment of diabetes, obesity, longevity, etc.

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Zbtb7c is a critical gluconeogenic transcription factor that induces glucose-6-phosphatase and phosphoenylpyruvate carboxykinase 1 genes expression during mice fasting

Cited by 14 publications

References 39 publications

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Identification of Novel Alzheimer’s Disease Loci Using Sex-Specific Family-Based Association Analysis of Whole-Genome Sequence Data

Hepatic transcriptional responses to fasting and feeding

Proto-oncoprotein Zbtb7c and SIRT1 repression: implications in high-fat diet-induced and age-dependent obesity

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