RRC ID 52164
Author Fukuhara M, Ma Y, Nagasawa K, Toyoshima F.
Title A G-quadruplex structure at the 5' end of the H19 coding region regulates H19 transcription.
Journal Sci Rep
Abstract The H19 gene, one of the best known imprinted genes, encodes a long non-coding RNA that regulates cell proliferation and differentiation. H19 RNA is widely expressed in embryonic tissues, but its expression is restricted in only a few tissues after birth. However, regulation of H19 gene expression remains poorly understood outside the context of genomic imprinting. Here we identified evolutionarily conserved guanine (G)-rich repeated motifs at the 5' end of the H19 coding region that are consistent with theoretically deduced G-quadruplex sequences. Circular dichroism spectroscopy and electrophoretic mobility shift assays with G-quadruplex-specific ligands revealed that the G-rich motif, located immediately downstream of the transcription start site (TSS), forms a G-quadruplex structure in vitro. By using a series of mutant forms of H19 harboring deletion or G-to-A substitutions, we found that the H19-G-quadruplex regulates H19 gene expression. We further showed that transcription factors Sp1 and E2F1 were associated with the H19-G-quadruplex to either suppress or promote the H19 transcription, respectively. Moreover, H19 expression during differentiation of mouse embryonic stem cells appears to be regulated by a genomic H19 G-quadruplex. These results demonstrate that the G-quadruplex structure immediately downstream of the TSS functions as a novel regulatory element for H19 gene expression.
Volume 8
Pages 45815
Published 2017-4-3
DOI 10.1038/srep45815
PII srep45815
PMID 28367967
PMC PMC5377947
MeSH Animals Circular Dichroism DNA Methylation / genetics E2F1 Transcription Factor / genetics G-Quadruplexes* Gene Expression Regulation / genetics Genomic Imprinting / genetics* Guanine / metabolism Humans Mice Nucleotide Motifs / genetics* Open Reading Frames / genetics Promoter Regions, Genetic / genetics RNA, Long Noncoding / genetics* Sequence Deletion / genetics Sp1 Transcription Factor / genetics Transcription Initiation Site
IF 3.998
Times Cited 10
Human and Animal Cells OLV2-1(AES0153)