Abstract:
:Mammalian antibody switch regions (∼1500 bp) are composed of a series of closely neighboring G4-capable sequences. Whereas numerous structural and genome-wide analyses of roles for minimal G4s in transcriptional regulation have been reported, Long G4-capable regions (LG4s)-like those at antibody switch regions-remain virtually unexplored. Using a novel computational approach we have identified 301 LG4s in the human genome and find LG4s prone to mutation and significantly associated with chromosomal rearrangements in malignancy. Strikingly, 217 LG4s overlap annotated enhancers, and we find the promoters regulated by these enhancers markedly enriched in G4-capable sequences suggesting G4s facilitate promoter-enhancer interactions. Finally, and much to our surprise, we also find single-stranded loops of minimal G4s within individual LG4 loci are frequently highly complementary to one another with 178 LG4 loci averaging >35 internal loop:loop complements of >8 bp. As such, we hypothesized (then experimentally confirmed) that G4 loops within individual LG4 loci directly basepair with one another (similar to characterized stem-loop kissing interactions) forming a hitherto undescribed, higher-order, G4-based secondary structure we term a 'G4 Kiss or G4K'. In conclusion, LG4s adopt novel, higher-order, composite G4 structures directly contributing to the inherent instability, regulatory capacity, and maintenance of these conspicuous genomic regions.
journal_name
Nucleic Acids Resjournal_title
Nucleic acids researchauthors
Williams JD,Houserova D,Johnson BR,Dyniewski B,Berroyer A,French H,Barchie AA,Bilbrey DD,Demeis JD,Ghee KR,Hughes AG,Kreitz NW,McInnis CH,Pudner SC,Reeves MN,Stahly AN,Turcu A,Watters BC,Daly GT,Langley RJ,Gillespdoi
10.1093/nar/gkaa357subject
Has Abstractpub_date
2020-06-19 00:00:00pages
5907-5925issue
11eissn
0305-1048issn
1362-4962pii
5834579journal_volume
48pub_type
杂志文章abstract::WorfDB (Worm ORFeome DataBase; http://worfdb.dfci.harvard.edu) was created to integrate and disseminate the data from the cloning of complete set of approximately 19 000 predicted protein-encoding Open Reading Frames (ORFs) of Caenorhabditis elegans (also referred to as the 'worm ORFeome'). WorfDB serves as a central ...
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