A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.

@article{citeulike:2470509, abstract = {Dicer initiates RNA interference by generating small RNAs involved in various silencing pathways. Dicer participates in centromeric silencing, but its role in the epigenetic regulation of other chromatin domains has not been explored. Here we show that Dicer1 deficiency in Mus musculus leads to decreased DNA methylation, concomitant with increased telomere recombination and telomere elongation. These DNA-methylation defects correlate with decreased expression of Dnmt1, Dnmt3a and Dnmt3b DNA methyltransferases (Dnmts), and methylation levels can be recovered by their overexpression. We identify the retinoblastoma-like 2 protein (Rbl2) as responsible for decreased Dnmt expression in Dicer1-null cells, suggesting the existence of Dicer-dependent small RNAs that target Rbl2. We identify the miR-290 cluster as being downregulated in Dicer1-deficient cells and show that it silences Rbl2, thereby controlling Dnmt expression. These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis.}, address = {Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), 3 Melchor Fern\'{a}ndez Almagro, Madrid E-28029, Spain.}, author = {Benetti, Roberta and Gonzalo, Susana and Jaco, Isabel and Mu\~{n}oz, Purificaci\'{o}n and Gonzalez, Susana and Schoeftner, Stefan and Murchison, Elizabeth and Andl, Thomas and Chen, Taiping and Klatt, Peter and Li, En and Serrano, Manuel and Millar, Sarah and Hannon, Gregory and Blasco, Maria A A. }, citeulike-article-id = {2470509}, doi = {10.1038/nsmb.1399}, issn = {1545-9985}, journal = {Nat Struct Mol Biol}, keywords = {epigenetics, methylation, mir-290\_cluster}, month = {March}, posted-at = {2008-03-10 10:38:06}, priority = {2}, title = {A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases.}, url = {http://dx.doi.org/10.1038/nsmb.1399}, year = {2008} }

TY - JOUR ID - citeulike:2470509 L3 - citeulike-article-id:2470509 TI - A mammalian microRNA cluster controls DNA methylation and telomere recombination via Rbl2-dependent regulation of DNA methyltransferases. JF - Nat Struct Mol Biol AD - Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Centre (CNIO), 3 Melchor Fernández Almagro, Madrid E-28029, Spain. SN - 1545-9985 N2 - Dicer initiates RNA interference by generating small RNAs involved in various silencing pathways. Dicer participates in centromeric silencing, but its role in the epigenetic regulation of other chromatin domains has not been explored. Here we show that Dicer1 deficiency in Mus musculus leads to decreased DNA methylation, concomitant with increased telomere recombination and telomere elongation. These DNA-methylation defects correlate with decreased expression of Dnmt1, Dnmt3a and Dnmt3b DNA methyltransferases (Dnmts), and methylation levels can be recovered by their overexpression. We identify the retinoblastoma-like 2 protein (Rbl2) as responsible for decreased Dnmt expression in Dicer1-null cells, suggesting the existence of Dicer-dependent small RNAs that target Rbl2. We identify the miR-290 cluster as being downregulated in Dicer1-deficient cells and show that it silences Rbl2, thereby controlling Dnmt expression. These results identify a pathway by which miR-290 directly regulates Rbl2-dependent Dnmt expression, indirectly affecting telomere-length homeostasis. KW - epigenetics KW - methylation KW - mir-290_cluster AU - Benetti, Roberta AU - Gonzalo, Susana AU - Jaco, Isabel AU - Muñoz, Purificación AU - Gonzalez, Susana AU - Schoeftner, Stefan AU - Murchison, Elizabeth AU - Andl, Thomas AU - Chen, Taiping AU - Klatt, Peter AU - Li, En AU - Serrano, Manuel AU - Millar, Sarah AU - Hannon, Gregory AU - Blasco, Maria A PY - 2008/03/02/ UR - http://dx.doi.org/10.1038/nsmb.1399 ER -