scholarly journals The Molecular Characteristics of the FAM13A Gene and the Role of Transcription Factors ACSL1 and ASCL2 in Its Core Promoter Region

Genes ◽  
2019 ◽  
Vol 10 (12) ◽  
pp. 981 ◽  
Author(s):  
Chengcheng Liang ◽  
Anning Li ◽  
Sayed Haidar Abbas Raza ◽  
Rajwali Khan ◽  
Xiaoyu Wang ◽  
...  

The gene family with sequence similarity 13 member A (FAM13A) has recently been identified as a marker gene in insulin sensitivity and lipolysis. In this study, we first analyzed the expression patterns of this gene in different tissues of adult cattle and then constructed a phylogenetic tree based on the FAM13A amino acid sequence. This showed that subcutaneous adipose tissue had the highest expression in all tissues except lung tissue. Then we summarized the gene structure. The promoter region sequence of the gene was successfully amplified, and the −241/+54 region has been identified as the core promoter region. The core promoter region was determined by the unidirectional deletion of the 5’ flanking promoter region of the FAM13A gene. Based on the bioinformatics analysis, we examined the dual luciferase activity of the vector constructed by the mutation site, and the transcription factors ACSL1 and ASCL2 were found as transcriptional regulators of FAM13A. Moreover, electrophoretic mobility shift assay (EMSA) further validated the regulatory role of ACSL1 and ASCL2 in the regulation of FAM13A. ACSL1 and ASCL2 were finally identified as activating transcription factors. Our results provide a basis for the function of the FAM13A gene in bovine adipocytes in order to improve the deposition of fat deposition in beef cattle muscle.

1992 ◽  
Vol 12 (3) ◽  
pp. 1352-1356 ◽  
Author(s):  
D C Leitman ◽  
E R Mackow ◽  
T Williams ◽  
J D Baxter ◽  
B L West

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.


1992 ◽  
Vol 12 (3) ◽  
pp. 1352-1356
Author(s):  
D C Leitman ◽  
E R Mackow ◽  
T Williams ◽  
J D Baxter ◽  
B L West

Activators of protein kinase C, such as 12-O-tetradecanoylphorbol 13-acetate (TPA), are known to regulate the expression of many genes, including the tumor necrosis factor alpha (TNF) gene, by affecting the level or activity of upstream transcription factors. To investigate the mechanism whereby TPA activates the TNF promoter, a series of 5'-deletion mutants of the human TNF promoter linked to chloramphenicol acetyltransferase was transfected into U937 human promonocytic cells. TPA produced a 7- to 11-fold activation of all TNF promoters tested, even those promoters truncated to contain only the core promoter with no upstream enhancer elements. The proximal TNF promoter containing only 28 nucleotides upstream and 10 nucleotides downstream of the RNA start site confers TPA activation to a variety of unrelated upstream enhancer elements and transcription factors, including Sp1, CTF/NF1, cyclic AMP-response element, GAL-E1a, and GAL-VP16. The level of activation by TPA depends on the TATA box structure, since the TPA response is greater in promoters containing the sequence TATAAA than in those containing TATTAA or TATTTA. These findings suggest that the core promoter region is a target for gene regulation by second-messenger pathways.


2021 ◽  
Author(s):  
Suzhen Lin ◽  
Ruinan Shen ◽  
Hong Pan ◽  
Lu He ◽  
Fang Fang ◽  
...  

Abstract BackgroundNeuroinflammation is known to be involved in the pathogenesis of Parkinson's disease (PD). Abnormal activation of microglia plays a key role in this pathological process. CD200R1 is a membrane glycoprotein primarily expressed in microglia in central nervous system responsible for transducing signaling maintaining microglia in stationary status. Our previous studies have demonstrated the dysregulation of CD200R1 and its involvement in PD pathogenesis. The binding of transcription factors with promoter regions is the basic and essential step for the regulation of gene expression. However, little is known about the human CD200R1 promoter region and the mechanism of the dysregulated expression of CD200R1 in PD. MethodsLuciferase reporter system was initially employed to identify the core region of CD200R1 promoter and figure out its potential transcription factors. Subsequently, we investigated the interaction adopting electrophoretic mobility shift assay and chromatin immunoprecipitation assay. The regulatory function of the detected transcription factors were further proved through its down-regulation and overexpression. We then collected the peripheral blood mononuclear cells from both PD patients and their healthy counterparts with matched age and sex to evaluate whether consistent results existed under clinical setting. Ultimately, the mouse model was established through knocking-out the identified transcription factor and its role in neuroinflammation and pathogenesis of PD was explored. ResultsWe defined that the core promoter region of CD200R was located within -482 to -146 bp upstream of the translation initiation site (TIS). In addition, we demonstrated that NFKB1 directly bound to the CD200R1 core promoter region and regulated its transcriptional activity. Besides, the expression of NFKB1 and CD200R1 was significantly correlated in human peripheral blood mononuclear cells and knocking down NFKB1 significantly reduced CD200R1 expression. Moreover, both NFKB1 and CD200R1 were significantly downregulated in samples from PD patients. Furthermore, NFKB1-/- mice exhibited exacerbated microglia activation and dopaminergic neuron loss after MPTP treatment. ConclusionOur study provided novel understanding of the transcriptional regulation of CD200R1 and its role in microglia homeostasis in the pathogenesis of PD.


Genes ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 182 ◽  
Author(s):  
Heléne Norder ◽  
Theogene Twagirumugabe ◽  
Joanna Said ◽  
Yarong Tian ◽  
Ka-Wei Tang ◽  
...  

Hepatitis B virus (HBV) is endemic in Rwanda and is a major etiologic agent for chronic liver disease in the country. In a previous analysis of HBV strains from Rwanda, the S genes of most strains segregated into one single clade of subgenotype, A1. More than half (55%) of the anti-HBe positive individuals were viremic. In this study, 23 complete HBV genomes and the core promoter region (CP) from 18 additional strains were sequenced. Phylogenetic analysis of complete genomes confirmed that most Rwandan strain formed a single unique clade, within subgenotype A1. Strains from 17 of 22 (77%) anti-HBe positive HBV carriers had either mutated the precore start codon (9 strains with either CUG, ACG, UUG, or AAG) or mutations in the Kozak sequence preceding the pre-core start codon (8 strains). These mutually exclusive mutations were also identified in subgenotypes A1 (70/266; 26%), A2 (12/255; 5%), and A3 (26/49; 53%) sequences from the GenBank. The results showed that previous, rarely described HBV variants, expressing little or no HBeAg, are selected in anti-HBe positive subgenotype Al carriers from Rwanda and that mutations reducing HBeAg synthesis might be unique for a particular HBV clade, not just for a specific genotype or subgenotype.


1996 ◽  
Vol 49 (2) ◽  
pp. 115-123 ◽  
Author(s):  
Masayuki Kurosaki ◽  
Nobuyuki Enomoto ◽  
Yasuhiro Asahina ◽  
Ikuo Sakuma ◽  
Takaaki Ikeda ◽  
...  

1994 ◽  
Vol 20 (6) ◽  
pp. 837-841 ◽  
Author(s):  
Tomasz Laskus ◽  
Jorge Rakela ◽  
Myron J. Tong ◽  
Marek J. Nowicki ◽  
James W. Mosley ◽  
...  

2004 ◽  
Vol 279 (27) ◽  
pp. 28789-28797 ◽  
Author(s):  
Tomoki Aoyama ◽  
Takeshi Okamoto ◽  
Satoshi Nagayama ◽  
Koichi Nishijo ◽  
Tatsuya Ishibe ◽  
...  

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