Loss of human ribosomal gene CpG methylation enhances cryptic RNA polymerase II transcription and disrupts ribosomal RNA processing. Export

@article{citeulike:5666867, abstract = {Epigenetic methyl-CpG silencing of the ribosomal RNA (rRNA) genes is thought to downregulate rRNA synthesis in mammals. In contrast, we now show that CpG methylation in fact positively influences rRNA synthesis and processing. Human HCT116 cells, inactivated for DNMT1 and DNMT3b or treated with aza-dC, lack CpG methylation and reactivate a large fraction of normally silent rRNA genes. Unexpectedly, these cells display reduced rRNA synthesis and processing and accumulate unprocessed 45S rRNA. Reactivation of the rRNA genes is associated with their cryptic transcription by RNA polymerase II. Ectopic expression of cryptic rRNA gene transcripts recapitulates the defects associated with loss of CpG methylation. The data demonstrate that rRNA gene silencing prevents cryptic RNA polymerase II transcription of these genes. Lack of silencing leads to the partial disruption of rRNA synthesis and rRNA processing, providing an explanation for the cytotoxic effects of loss of CpG methylation.}, author = {Gagnon-Kugler, Th\'{e}r\`{e}se and Langlois, Fr\'{e}d\'{e}ric and Stefanovsky, Victor and Lessard, Fr\'{e}d\'{e}ric and Moss, Tom}, citeulike-article-id = {5666867}, citeulike-linkout-0 = {http://dx.doi.org/10.1016/j.molcel.2009.07.008}, citeulike-linkout-1 = {http://linkinghub.elsevier.com/retrieve/pii/S1097276509005036}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19716787}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19716787}, day = {28}, doi = {10.1016/j.molcel.2009.07.008}, issn = {1097-4164}, journal = {Molecular cell}, keywords = {cpg, cryptic, polymerase}, month = {August}, number = {4}, pages = {414--425}, posted-at = {2009-09-11 20:15:47}, priority = {4}, title = {Loss of human ribosomal gene CpG methylation enhances cryptic RNA polymerase II transcription and disrupts ribosomal RNA processing.}, url = {http://dx.doi.org/10.1016/j.molcel.2009.07.008}, volume = {35}, year = {2009} }

TY - JOUR ID - citeulike:5666867 L3 - citeulike-article-id:5666867 N2 - Epigenetic methyl-CpG silencing of the ribosomal RNA (rRNA) genes is thought to downregulate rRNA synthesis in mammals. In contrast, we now show that CpG methylation in fact positively influences rRNA synthesis and processing. Human HCT116 cells, inactivated for DNMT1 and DNMT3b or treated with aza-dC, lack CpG methylation and reactivate a large fraction of normally silent rRNA genes. Unexpectedly, these cells display reduced rRNA synthesis and processing and accumulate unprocessed 45S rRNA. Reactivation of the rRNA genes is associated with their cryptic transcription by RNA polymerase II. Ectopic expression of cryptic rRNA gene transcripts recapitulates the defects associated with loss of CpG methylation. The data demonstrate that rRNA gene silencing prevents cryptic RNA polymerase II transcription of these genes. Lack of silencing leads to the partial disruption of rRNA synthesis and rRNA processing, providing an explanation for the cytotoxic effects of loss of CpG methylation. IS - 4 JF - Molecular cell SN - 1097-4164 EP - 425 TI - Loss of human ribosomal gene CpG methylation enhances cryptic RNA polymerase II transcription and disrupts ribosomal RNA processing. VL - 35 SP - 414 KW - cpg KW - cryptic KW - polymerase AU - Gagnon-Kugler, Thérèse AU - Langlois, Frédéric AU - Stefanovsky, Victor AU - Lessard, Frédéric AU - Moss, Tom PY - 2009/08/28/ UR - http://dx.doi.org/10.1016/j.molcel.2009.07.008 ER -