The female-biased factor VGLL3 drives cutaneous and systemic autoimmunity

Billi, Allison C.; Gharaee−Kermani, Mehrnaz; Fullmer, Joseph; Tsoi, Lam C.; Hill, Brett; Gruszka, Dennis; Ludwig, J.; Xing, Xianying; Estadt, Shannon N.; Wolf, Sonya; Rizvi, Syed Monem; Berthier, Céline C.; Hodgin, Jeffrey B.; Beamer, Maria A.; Sarkar, Mrinal K.; Liang, Yun; Uppala, Rattapon; Shao, Shuai; Zeng, Chang; Harms, Paul W.; Verhaegen, Monique; Voorhees, John J.; Wen, Fei; Ward, Nicole L.; Dlugosz, Andrzej A.; Kahlenberg, J. Michelle; Guðjónsson, Jóhann E.

doi:10.1172/jci.insight.127291

Cited by 56 publications

(46 citation statements)

References 36 publications

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“…Evolutionarily, females have a greater amount of VGLL3, which is a unique transcription factor that regulates genes and has a firm association with autoimmune diseases such as Sjogren's syndrome, SLE, and scleroderma [15]. VGLL3 elicits a cutaneous inflammatory response in SLE patients such as a butterfly skin rash across their cheeks and nose, by upregulating inflammatory genes [16]. In the following experiment conducted in which the VGLL3 transcription factor of humans was reviewed under high-resolution global transcription analyses regarding its relation to autoimmune disorders.…”

Section: Vgll3 Transcription Factormentioning

confidence: 99%

The Prevalence of Autoimmune Disorders in Women: A Narrative Review

Angum¹,

Khan²,

Kaler³

et al. 2020

Cureus

208

136

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Autoimmune disorders are characterized as a condition in which the host's immune system mistakenly attacks itself. These disorders cause the immune system to cause a systemic reaction by attacking multiple organs or may be localized to attacking one specific organ, such as the skin. The exact mechanism of such autoimmune conditions is not well understood; however, the presumed mechanism tends to vary amongst the disorders. Autoimmune diseases present with a clear gender bias with a greater prevalence amongst women, occurring at a rate of 2 to 1. Many autoimmune disorders tend to affect women during periods of extensive stress, such as pregnancy, or during a great hormonal change. A far greater number of women are affected every year with autoimmune diseases, leading to researchers attempting to identify the underlying factors, which could be responsible for this disparity. Autoimmune disorders occur as a result of multiple factors as some disorders may be genetic, while others are sporadic. Throughout this review, various hypotheses are explored that provide insight into the increased susceptibility of autoimmune disorders within women.

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Section: Vgll3 Transcription Factormentioning

confidence: 99%

The Prevalence of Autoimmune Disorders in Women: A Narrative Review

Angum¹,

Khan²,

Kaler³

et al. 2020

Cureus

208

136

View full text Add to dashboard Cite

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“…44,45 In the context of the prominent inflammatory infiltrate in MIFS it is of interest that increased expression of Vgll3 in mice drives a proinflammatory gene expression program. 46 In conclusion, we show that MIFS is a genetically heterogeneous sarcoma displaying considerable overlap with other sarcoma subtypes.…”

Section: Discussionmentioning

confidence: 57%

“…The function of VGLL3 is still not very well understood, but it is thought to be a transcription co‐factor and has been implicated in both muscle and fat cell differentiation . In the context of the prominent inflammatory infiltrate in MIFS it is of interest that increased expression of Vgll3 in mice drives a proinflammatory gene expression program …”

Section: Discussionmentioning

confidence: 99%

Deep sequencing of myxoinflammatory fibroblastic sarcoma

Arbajian

Hofvander

Magnusson

et al. 2020

Genes Chromosomes & Cancer

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Myxoinflammatory fibroblastic sarcoma (MIFS) has recurrent genetic features in the form of a translocation t(1;10)(p22‐31;q24‐25), BRAF gene fusions, and/or an amplicon in 3p11‐12 including the VGLL3 gene. The breakpoints on chromosomes 1 and 10 in the t(1;10) cluster in or near the TGFBR3 and OGA genes, respectively. We here used a combination of deep sequencing of the genome (WGS), captured sequences (Cap‐seq), and transcriptome (RNA‐seq) and genomic arrays to investigate the molecular outcome of the t(1;10) and the VGLL3 amplicon, as well as to assess the spectrum of other recurrent genomic features in MIFS. Apart from a ROBO1‐BRAF chimera in a t(1;10)‐negative MIFS‐like tumor, no fusion gene was found at RNA‐seq. This was in line with WGS and Cap‐seq results, revealing variable breakpoints in chromosomes 1 and 10 and genomic breakpoints that should not yield functional fusion transcripts. The most common genomic rearrangements were breakpoints in or around the OGA, NPM3, and FGF8 genes in chromosome band 10q24, and loss of 1p11‐p21 and 10q26‐qter (all simultaneously present in 6/7 MIFS); a breakpoint in or near TGFBR3 in chromosome 1 was found in four of these tumors. Amplification and overexpression of VGLL3 was a consistent feature in MIFS and MIFS‐like tumors with amplicons in 3p11‐12. The significant molecular genetic outcome of the recurrent t(1;10) could be loss of genetic material from 1p and 10q. Other recurrent genomic imbalances in MIFS, such as homozygous loss of CDKN2A and 3p‐ and 13q‐deletions, are shared with other sarcomas, suggesting overlapping pathogenetic pathways.

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“…VGLL3-high gastric tumor showed the activation of the MAPK, JAK-STAT, and WNT pathways together with enhanced immune infiltrates (57). These features in VGLL3-high tumors may reflect the proinflammatory functions of VGLL3 which were found in VGLL3-overexpressing mice (58). Transforming growth factor-β (TGF-β) induced VGLL3 expression in a histone modification-dependent manner (59).…”

Section: Vgll3 Is Involved In Both Tumor Development and Suppressionmentioning

confidence: 99%

Multiple Roles of Vestigial-Like Family Members in Tumor Development

Yamaguchi

2020

Front. Oncol.

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Vestigial-like family (VGLL) members are mammalian orthologs of vestigial gene in Drosophila, and they consist of four homologs (VGLL1-4). VGLL members have TDU motifs that are binding regions to TEA/ATSS-DNA-binding domain transcription factor (TEAD). Through TDU motifs, VGLL members act as transcriptional cofactors for TEAD. VGLL1-3 have single TDU motif, whereas VGLL4 has two tandem TDU motifs, suggesting that VGLL4 has distinct molecular functions among this family. Although molecular and physiological functions of VGLL members are still obscure, emerging evidence has shown that these members are involved in tumor development. Gene alterations and elevated expression of VGLL1-3 were observed in various types of tumors, and VGLL1-3 have been shown to possess tumorigenic functions. In contrast, down-regulation of VGLL4 was detected in various tumors, and the tumor-suppressing role of VGLL4 has been demonstrated. In this review, we summarize the recently identified multiple roles of VGLL members in tumor development and provide important and novel insights regarding tumorigenesis.

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The female-biased factor VGLL3 drives cutaneous and systemic autoimmunity

Cited by 56 publications

References 36 publications

The Prevalence of Autoimmune Disorders in Women: A Narrative Review

The Prevalence of Autoimmune Disorders in Women: A Narrative Review

Deep sequencing of myxoinflammatory fibroblastic sarcoma

Multiple Roles of Vestigial-Like Family Members in Tumor Development

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