ZNF300, a recently identified human transcription factor, activates the human IL-2Rβ promoter through the overlapping ZNF300/EGR1 binding site

Lü, Xue; Qiu, Hongling; Ma, Jian; Guo, Mingxiong; Li, Wenxin

doi:10.2478/s11658-010-0025-1

Cited by 6 publications

(11 citation statements)

References 17 publications

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“…3 Functions of significantly differentially expressed genes in placenta. Venn diagrams of function categories for DEGs with known gene ontologies [ 39 , 84 , 85 , 93 , 97 , 98 , 100 – 106 , 114 – 126 ]. Autosome genes are underlined.…”

Section: Resultsmentioning

confidence: 99%

“…Differentially expressed transcription factors in first trimester may explain sex differences in later pregnancy complications. For example, ZNF300 (1.58-fold upregulated in females) encodes a transcription factor protein that shares DNA binding sites with Early growth response 1 (Egr1), a zinc finger transcription factor that is elevated in placentas of pregnancies that later develop preeclampsia, which is more common in pregnancies with a male fetus [ 15 , 106 , 107 ]. Increased expression of ZNF300 in females may function as a competitor of EGR1 binding sites, leading to reduced rates of preeclampsia.…”

Section: Discussionmentioning

confidence: 99%

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Sex differences in the late first trimester human placenta transcriptome

et al. 2018

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BackgroundDevelopment of the placenta during the late first trimester is critical to ensure normal growth and development of the fetus. Developmental differences in this window such as sex-specific variation are implicated in later placental disease states, yet gene expression at this time is poorly understood.MethodsRNA-sequencing was performed to characterize the transcriptome of 39 first trimester human placentas using chorionic villi following genetic testing (17 females, 22 males). Gene enrichment analysis was performed to find enriched canonical pathways and gene ontologies in the first trimester. DESeq2 was used to find sexually dimorphic gene expression. Patient demographics were analyzed for sex differences in fetal weight at time of chorionic villus sampling and birth.ResultsRNA-sequencing analyses detected 14,250 expressed genes, with chromosome 19 contributing the greatest proportion (973/2852, 34.1% of chromosome 19 genes) and Y chromosome contributing the least (16/568, 2.8%). Several placenta-enriched genes as well as histone-coding genes were identified to be unique to the first trimester and common to both sexes. Further, we identified 58 genes with significantly different expression between males and females: 25 X-linked, 15 Y-linked, and 18 autosomal genes. Genes that escape X inactivation were highly represented (59.1%) among X-linked genes upregulated in females. Many genes differentially expressed by sex consisted of X/Y gene pairs, suggesting that dosage compensation plays a role in sex differences. These X/Y pairs had roles in parallel, ancient canonical pathways important for eukaryotic cell growth and survival: chromatin modification, transcription, splicing, and translation.ConclusionsThis study is the first characterization of the late first trimester placenta transcriptome, highlighting similarities and differences among the sexes in ongoing human pregnancies resulting in live births. Sexual dimorphism may contribute to pregnancy outcomes, including fetal growth and birth weight, which was seen in our cohort, with males significantly heavier than females at birth. This transcriptome provides a basis for development of early diagnostic tests of placental function that can indicate overall pregnancy heath, fetal-maternal health, and long-term adult health.Electronic supplementary materialThe online version of this article (10.1186/s13293-018-0165-y) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Sex differences in the late first trimester human placenta transcriptome

et al. 2018

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“…We next explored how ZNF300 regulate the NF‐κB pathway. Our previous study had indicated the presence of putative ZNF300 binding sites (C(t/a)GGGGG(g/c)G) in the promoter regions of genes such as IL2RB , CD44 and TRAF2 [17, 18]. Here, we focused on the putative ZNF300 binding site in the proximity of the promoter of the gene‐encoding TRAF2 (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…binding sites (C(t/a)GGGGG(g/c)G) in the promoter regions of genes such as IL2RB, CD44 and TRAF2 [17,18]. Here, we focused on the putative ZNF300 binding site in the proximity of the promoter of the gene-encoding TRAF2 (Fig.…”

Section: Znf300 Regulates Transcription Of Traf2mentioning

confidence: 99%

Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF‐kB pathway

Wang¹,

Wang²,

Xu³

et al. 2012

J Cellular Molecular Medi

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Zinc finger proteins (ZNF) play important roles in various physiological processes. Here we report that ZNF300, a novel zinc finger protein, identified specifically in humans, promotes tumour development by modulating the NF-κB pathway. Inflammatory factors were found to induce ZNF300 expression in HeLa cell line, and ZNF300 expression further enhanced NF-κB signalling by activating TRAF2 and physically interacting with IKKβ. Furthermore, ZNF300 overexpression increased ERK1/2 phosphorylation and the expression of c-myc, IL-6, and IL-8 but decreased the expression of p21waf-1 and p27Kip1; whose down-regulation led to the opposite effect. Most importantly, ZNF300 overexpression stimulated cancer cell proliferation in vitro and significantly enhanced tumour development and metastasis in mouse xenograft model, while knocking down ZNF300 led to the opposite effects. We have identified a novel function for ZNF300 in tumour development that may uniquely link inflammation and NF-κB to tumourigenesis in humans but not in mice.

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“… 74 , 75 Another blood-specific eQTL includes ZNF300, which is downregulated by Crohn risk allele and is involved in activating the IL2βR expressed highly on T-regulatory cells. 76 Other identified eQTLs were involved in T-cell skewing. For example, FOSL2 is an AP1 transcription factor, which is a putative regulator of plasticity and repressor of TH17 cells.…”

Section: Discussionmentioning

confidence: 99%

Blood and Intestine eQTLs from an Anti-TNF-Resistant Crohn's Disease Cohort Inform IBD Genetic Association Loci

Narzo

Peters

Argmann

et al. 2016

Clinical and Translational Gastroenterology

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OBJECTIVES:Genome-wide association studies (GWAS) have identified loci reproducibly associated with inflammatory bowel disease (IBD) and other immune-mediated diseases; however, the molecular mechanisms underlying most of genetic susceptibility remain undefined. Expressional quantitative trait loci (eQTL) of disease-relevant tissue can be employed in order to elucidate the genes and pathways affected by disease-specific genetic variance.METHODS:In this study, we derived eQTLs for human whole blood and intestine tissues of anti-tumor necrosis factor-resistant Crohn's disease (CD) patients. We interpreted these eQTLs in the context of published IBD GWAS hits to inform on the disease process.RESULTS:At 10% false discovery rate, we discovered that 5,174 genes in blood and 2,063 genes in the intestine were controlled by a nearby single-nucleotide polymorphism (SNP) (i.e., cis-eQTL), among which 1,360 were shared between the two tissues. A large fraction of the identified eQTLs were supported by the regulomeDB database, showing that the eQTLs reside in regulatory elements (odds ratio; OR=3.44 and 3.24 for blood and intestine eQTLs, respectively) as opposed to protein-coding regions. Published IBD GWAS hits as a whole were enriched for blood and intestine eQTLs (OR=2.88 and 2.05; and P value=2.51E-9 and 0.013, respectively), thereby linking genetic susceptibility to control of gene expression in these tissues. Through a systematic search, we used eQTL data to inform 109 out of 372 IBD GWAS SNPs documented in National Human Genome Research Institute catalog, and we categorized the genes influenced by eQTLs according to their functions. Many of these genes have experimentally validated roles in specific cell types contributing to intestinal inflammation.CONCLUSIONS:The blood and intestine eQTLs described in this study represent a powerful tool to link GWAS loci to a regulatory function and thus elucidate the mechanisms underlying the genetic loci associated with IBD and related conditions. Overall, our eQTL discovery approach empirically identifies the disease-associated variants including their impact on the direction and extent of expression changes in the context of disease-relevant cellular pathways in order to infer the functional outcome of this aspect of genetic susceptibility.

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ZNF300, a recently identified human transcription factor, activates the human IL-2Rβ promoter through the overlapping ZNF300/EGR1 binding site

Cited by 6 publications

References 17 publications

Sex differences in the late first trimester human placenta transcriptome

Sex differences in the late first trimester human placenta transcriptome

Overexpression of the human ZNF300 gene enhances growth and metastasis of cancer cells through activating NF‐kB pathway

Blood and Intestine eQTLs from an Anti-TNF-Resistant Crohn's Disease Cohort Inform IBD Genetic Association Loci

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