Publication Date:
2013-10-11
Description:
DNA methylation was first described almost a century ago; however, the rules governing its establishment and maintenance remain elusive. Here we present data demonstrating that active transcription regulates levels of genomic methylation. We identify a novel RNA arising from the CEBPA gene locus that is critical in regulating the local DNA methylation profile. This RNA binds to DNMT1 and prevents CEBPA gene locus methylation. Deep sequencing of transcripts associated with DNMT1 combined with genome-scale methylation and expression profiling extend the generality of this finding to numerous gene loci. Collectively, these results delineate the nature of DNMT1-RNA interactions and suggest strategies for gene-selective demethylation of therapeutic targets in human diseases.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870304/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3870304/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Di Ruscio, Annalisa -- Ebralidze, Alexander K -- Benoukraf, Touati -- Amabile, Giovanni -- Goff, Loyal A -- Terragni, Jolyon -- Figueroa, Maria Eugenia -- De Figueiredo Pontes, Lorena Lobo -- Alberich-Jorda, Meritxell -- Zhang, Pu -- Wu, Mengchu -- D'Alo, Francesco -- Melnick, Ari -- Leone, Giuseppe -- Ebralidze, Konstantin K -- Pradhan, Sriharsa -- Rinn, John L -- Tenen, Daniel G -- CA118316/CA/NCI NIH HHS/ -- CA66996/CA/NCI NIH HHS/ -- HL56745/HL/NHLBI NIH HHS/ -- P01 CA066996/CA/NCI NIH HHS/ -- R01 CA118316/CA/NCI NIH HHS/ -- R01 HL056745/HL/NHLBI NIH HHS/ -- R01 HL112719/HL/NHLBI NIH HHS/ -- T32 HL007917-11A1/HL/NHLBI NIH HHS/ -- England -- Nature. 2013 Nov 21;503(7476):371-6. doi: 10.1038/nature12598. Epub 2013 Oct 9.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Harvard Stem Cell Institute, Harvard Medical School, Boston, Massachusetts 02115, USA [2] Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA [3] Universita Cattolica del Sacro Cuore, Institute of Hematology, L.go A. Gemelli 8, Rome 00168, Italy [4].〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24107992" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
CCAAT-Enhancer-Binding Proteins/*genetics
;
Cell Line
;
DNA/genetics/metabolism
;
DNA (Cytosine-5-)-Methyltransferase/*metabolism
;
DNA Methylation/*genetics
;
Gene Expression Profiling
;
Gene Expression Regulation/*genetics
;
Genome, Human/genetics
;
Humans
;
RNA, Messenger/genetics/metabolism
;
RNA, Untranslated/genetics/*metabolism
;
RNA-Binding Proteins/metabolism
;
Substrate Specificity
;
Transcription, Genetic/genetics
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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