Long noncoding RNA-mediated maintenance of DNA methylation and transcriptional gene silencing.
Establishment of silencing by noncoding RNAs (ncRNAs) via targeting of chromatin remodelers is relatively well investigated; however, their role in the maintenance of silencing is poorly understood. Here, we explored the functional role of the long ncRNA Kcnq1ot1 in the maintenance of transcriptional gene silencing in the one mega-base Kcnq1 imprinted domain in a transgenic mouse model. By conditionally deleting the Kcnq1ot1 ncRNA at different stages of mouse development, we suggest that Kcnq1ot1 ncRNA is required for the maintenance of the silencing of ubiquitously imprinted genes (UIGs) at all developmental stages. In addition, Kcnq1ot1 ncRNA is also involved in guiding and maintaining the CpG methylation at somatic differentially methylated regions flanking the UIGs, which is a hitherto unknown role for a long ncRNA. On the other hand, silencing of some of the placental-specific imprinted genes (PIGs) is maintained independently of Kcnq1ot1 ncRNA. Interestingly, the non-imprinted genes (NIGs) that escape RNA-mediated silencing are enriched with enhancer-specific modifications. Taken together, this study illustrates the gene-specific maintenance mechanisms operational at the Kcnq1 locus for tissue-specific transcriptional gene silencing and activation.
Science for Life Laboratory, Department of Immunology, Genetics and Pathology, Dag Hammarskjölds Väg 20, Uppsala University, Uppsala, Sweden.
Faizaan
F
Mohammad
Gaurav Kumar
GK
Pandey
Tanmoy
T
Mondal
Stefan
S
Enroth
Lisa
L
Redrup
Ulf
U
Gyllensten
Chandrasekhar
C
Kanduri
D000818:Animals; D018899:CpG Islands / Q000235:genetics; D003433:Crosses, Genetic; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D020868:Gene Silencing; D018392:Genomic Imprinting; D006570:Heterochromatin / Q000378:metabolism; D006720:Homozygote; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D012313:RNA / Q000378:metabolism; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated / Q000235:genetics*; D013997:Time Factors
D006570:Heterochromatin; D051657:KCNQ1 Potassium Channel; C449939:KCNQ1OT1 RNA; C496910:Kcnq1 protein, mouse; D062085:RNA, Long Noncoding; D022661:RNA, Untranslated; D012313:RNA