この度、イギリスCambridgeからThe Babraham InstituteのGavin Kelsey先生に生体防御医学研究所でのセミナーをお願い致しました。このセミナーでは、トランスクリプトーム解析およびエピゲノム解析により得られた、卵子におけるゲノムインプリンティング機構に関する最新の知見についてお話しいただきます。講演は英語で行われます。ご来聴を歓迎致します。
|演題||Machanisms of DNA methylation establishment in female germ cells.
（seminar in English）
|演者||Dr. Gavin Kelsey
Principal Research Scientist
Epigenetics Programme, The Babraham Institute, Cambridge, UK
Jan. 19, 2012 (Thu), 15:00-16:00
|場所||馬出医学系キャンパス内 生体防御医学研究所 本館１階会議室
Medical Institute of Bioregulation, Main Building 1F, Seminar Room
No.21 on the following linked map
The mechanisms by which DNA methylation is established in mammalian cells are still poorly understood. Imprinted genes are an important model, as they are methylated in a gamete-specific manner and because in the female germline de novo methylation occurs in non-dividing cells. We are investigating why germline differentially methylated regions (gDMRs) of imprinted genes become methylated, whereas the great majority of CpG islands (CGIs) remain unmethylated. We have shown, using the imprinted Gnas locus, that transcription through gDMRs is required for their methylation in oocytes. We are testing whether a similar requirement applies at all maternally methylated gDMRs and whether the same principles also govern methylation of other CGIs in germ cells. Consistent with our model, mRNA-Seq analysis of growing oocytes at the onset of de novo methylation reveals that gDMRs at all maternally imprinted loci coincide with inactive promoters within active transcription units. Using reduced representation bisulphite sequencing (RRBS), an effective method for providing single base-pair resolution of methylation at CGIs, we identified >1000 CGIs methylated in mature oocytes. These CGIs depend on Dnmt3a and Dnmt3L for methylation, revealing a general role for Dnmt3L beyond imprinting. Methylated CGIs are not discriminated by sequence features, indicating that non-sequence based properties primarily determine their methylation. Instead, methylated CGIs are preferentially located in active transcription units and depleted in H3K4me3, supporting a general transcription-dependent mechanism of methylation. We propose that transcription remodels histone modifications at gDMRs to a state permissive to the DNMT3a:DNMT3L complex.
- Chotlalia, M. et al.
Transcription is required for establishment of germline methylation marks at imprinted genes. Genes & Dev. 23, 105-117, 2009
- Smallwood, S.A. et al.
Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat. Genet. 43, 811-814 , 2011
|連絡先||生体防御医学研究所 エピゲノム学分野 佐々木 裕之
Division of Epigenomics, MIB, Hiroyuki SASAKI