Document Detail

Natural antisense transcript for hyaluronan synthase 2 (HAS2-AS1) induces transcription of HAS2 via protein O-GlcNAcylation.
MedLine Citation:
PMID:  25183006     Owner:  NLM     Status:  Publisher    
Changes in the microenvironment organization within vascular walls are critical events in the pathogenesis of vascular pathologies, including atherosclerosis and restenosis. Hyaluronan (HA) accumulation into artery walls supports vessel thickening and is involved in many cardiocirculatory diseases. Excessive cytosolic glucose can enter the hexosamine biosynthetic pathway, increase UDP-N-acetylglucosamine (UDP-GlcNAc) availability, and lead to modification of cytosolic proteins via O-linked attachment of the monosaccharide β-N-GlcNAc (O-GlcNAcylation) from UDP-GlcNAc by the enzyme O-GlcNAc transferase (OGT). As many cytoplasmic and nuclear proteins can be glycosylated by O-GlcNAc, we studied whether the expression of the HA synthases (HASes) that synthesize HA could be controlled by O-GlcNAcylation in human aortic smooth muscle cells (AoSMCs). Among the three HAS isoenzymes, only HAS2 mRNA increased after O-GlcNAcylation induced by glucosamine treatments or by inhibiting OGT with PUGNAC. We found that the natural antisense transcript (NAT) of HAS2 (HAS2-AS1) was absolutely necessary to induce the transcription of the HAS2 gene. Moreover, we found that O-GlcNAcylation modulated HAS2-AS1 promoter activation by recruiting the NF-kB subunit p65, but not the HAS2 promoter, whereas HAS2-AS1 NAT, working in cis, regulated HAS2 transcription by altering the chromatin structure around the HAS2 proximal promoter via O-GlcNAcylation and acetylation. These results indicate that HAS2 transcription can be finely regulated not only by recruiting transcription factors to the promoter as previously described, but also by modulating chromatin accessibility by epigenetic modifications.
Davide Vigetti; Sara Deleonibus; Paola Moretto; Timothy Bowen; Jens W Fischer; Maria Grandoch; Alexander Oberhuber; Dona C Love; John A Hanover; Raffaella Cinquetti; Eugenia Karousou; Manuela Viola; Maria Luisa D'Angelo; Vincent C Hascall; Giancarlo De Luca; Alberto Passi
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-2
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  -     ISSN:  1083-351X     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2014, The American Society for Biochemistry and Molecular Biology.
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