研究課題
The eukaryotic genome is organized into eu- or hetero-chromatin domains, the former is gene-rich and transcriptionally active, while the latter is gene-poor and transcriptionally inactive. Eu- or hetero-chromatin are also analogous to A or B compartments, calculated from the PC1 (primary component 1) value of the eigenvector of the Hi-C (a method for chromatin conformation capture) matrix. During S phase, A compartments replicate early while B compartments replicate late. It is, however, not understood if A/B compartmentalization and early/late replication timing is mechanistically linked.
2: おおむね順調に進展している
The aim of this project is to determine if A/B compartments and early/late replication timing are mechanistically linked. By taking advantage of degron-based acute depletion of transcriptional machinery, I have found that transcriptional elongation functions as a molecular link to connect A/B compartments and early/late replication timing. Furthermore, by taking advantage of a conditional gene knockout strategy, I have been able to identify an epigenetic mechanism that functions directly downstream of transcriptional elongation to connect compartmentalization with replication timing. Finally, via genomics-based screening and genetic knock-in experiments, I have determined specific genetic sequences that play a key role in connecting A/B compartments with early/late replication timing.
My research reveals that in addition to regulating gene expression, transcription possesses distinct roles to regulate 3D genome and replication timing. Intriguingly, this role of transcription appears to be mediated by distinct epigenetic mechanisms that are deposited downstream of transcriptional elongation. In this project, I have focused on one such epigenetic mechanism that is enriched in A compartments and promotes early replication. By research, however, has unveiled several other epigenetic pathways that may also take part in regulation of the 3D genome and replication timing. Some of these epigenetic mechanisms are expected to be involved in regulation of B compartments and/or late replication timing. Further exploration of these mechanisms is my future goal.
The incurring amount will be used to perform additional experiments in next fiscal year.
すべて 2023 2022
すべて 雑誌論文 (4件) (うち国際共著 4件、 査読あり 3件)
Curr Opin Genet Dev .
巻: 80 ページ: Epub
10.1016/j.gde.2023.102035
Nat Commun.
巻: 13 (1) ページ: Online
10.1038/s41467-022-34856-8
10.1038/s41467-022-34779-4
Sci China Life Sci.
巻: 65 (7) ページ: 1445-1455
10.1007/s11427-021-2029-0
