scholarly journals The lupus susceptibility locus Sgp3 encodes the suppressor of endogenous retrovirus expression SNERV

2018 ◽  
Author(s):  
Rebecca S Treger ◽  
Scott D Pope ◽  
Yong Kong ◽  
Maria Tokuyama ◽  
Manabu Taura ◽  
...  

Elevated endogenous retrovirus (ERV) transcription and anti-ERV antibody reactivity are implicated in lupus pathogenesis. Overproduction of non-ecotropic ERV (NEERV) envelope glycoprotein, gp70, and resultant nephritis occur in lupus-prone mice. However, a NEERV repressor has not been identified to test if this association is causal. Here we identified suppressor of NEERV (Snerv) 1 & 2, Kruppel-associated box zinc finger proteins (KRAB-ZFP) that repressed NEERV by binding the NEERV long terminal repeat to recruit the transcriptional regulator KAP1. Germline Snerv1/2 deletion increased activating chromatin modifications, transcription, and gp70 expression from NEERV loci. F1 crosses of lupus-prone NZB and 129 mice to Snerv1/2-/- mice failed to restore NEERV repression, demonstrating that loss of SNERV underlies the lupus autoantigen gp70 overproduction that promotes nephritis in susceptible mice. Increased ERV expression in lupus patients was inversely correlated with expression of three putative ERV-suppressing KRAB-ZFP, suggesting that KRAB-ZFP-mediated ERV misexpression may contribute to human lupus pathogenesis.

2005 ◽  
Vol 25 (21) ◽  
pp. 9209-9220 ◽  
Author(s):  
Sara R. Heras ◽  
Manuel C. López ◽  
José Luis García-Pérez ◽  
Sandra L. Martin ◽  
M. Carmen Thomas

ABSTRACT L1Tc, a non-long terminal repeat retrotransposon from Trypanosoma cruzi, is a 4.9-kb actively transcribed element which contains a single open reading frame coding for the machinery necessary for its autonomous retrotransposition. In this paper, we analyze the protein encoded by the L1Tc 3′ region, termed C2-L1Tc, which contains two zinc finger motifs similar to those present in the TFIIIA transcription factor family. C2-L1Tc binds nucleic acids with different affinities, such that RNA > tRNA > single-stranded DNA > double-stranded DNA, without any evidence for sequence specificity. C2-L1Tc also exhibits nucleic acid chaperone activity on different DNA templates that may participate in the mechanism of retrotransposition of the element. C2-L1Tc promotes annealing of complementary oligonucleotides, prevents melting of perfect DNA duplexes, and facilitates the strand exchange between DNAs to form the most stable duplex DNA in competitive displacement assays. Mapping of regions of C2-L1Tc using specific peptides showed that nucleic acid chaperone activity required a short basic sequence accompanied by a zinc finger motif or by another basic region such as RRR. Thus, a short basic polypeptide containing the two C2H2 motifs promotes formation of the most stable duplex DNA at a concentration only three times higher than that required for C2-L1Tc.


Oncotarget ◽  
2018 ◽  
Vol 9 (31) ◽  
pp. 22069-22078 ◽  
Author(s):  
Masataka Shimonosono ◽  
Takaaki Arigami ◽  
Shigehiro Yanagita ◽  
Daisuke Matsushita ◽  
Yasuto Uchikado ◽  
...  

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hee-Eun Lee ◽  
Ara Jo ◽  
Jennifer Im ◽  
Hee-Jae Cha ◽  
Woo-Jin Kim ◽  
...  

Abstract Endogenous retroviruses (ERVs) have been identified at different copy numbers in various organisms. The long terminal repeat (LTR) element of an ERV has the capacity to exert regulatory influence as both a promoter and enhancer of cellular genes. Here, we describe olive flounder (OF)-ERV9, derived from chromosome 9 of the olive flounder. OF-ERV9-LTR provide binding sites for various transcription factors and showed enhancer activity. The OF-ERV9-LTR demonstrates high sequence similarity with the 3′ untranslated region (UTR) of various genes that also contain seed sequences (TGTTTTG) that bind the LTR-derived microRNA(miRNA), OF-miRNA-307. Additionally, OF-miRNA-307 collaborates with transcription factors located in OF-ERV9-LTR to regulate gene expression. Taken together, our data facilitates a greater understanding of the molecular function of OF-ERV families and suggests that OF-miRNA-307 may act as a super-enhancer miRNA regulating gene activity.


2012 ◽  
Vol 23 (9) ◽  
pp. 932-942 ◽  
Author(s):  
Supachai Sakkhachornphop ◽  
Carlos F. Barbas ◽  
Rassamee Keawvichit ◽  
Kanlaya Wongworapat ◽  
Chatchai Tayapiwatana

2012 ◽  
Vol 87 (1) ◽  
pp. 25-36 ◽  
Author(s):  
L. Xu ◽  
A. G. Elkahloun ◽  
F. Candotti ◽  
A. Grajkowski ◽  
S. L. Beaucage ◽  
...  

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