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DNA複製と遺伝子発現に関するセミナーのお知らせ



下記のセミナーを開催しますので是非御来聴下さい。
(問合せ先:東大・院理・生物科学専攻・平良眞規、03-5841-4434)

演題:Replication timing changes and transcriptional regulation during neural differentiation of mouse embryonic stem cells

演者:平谷 伊智朗 博士(Dr. Ichiro Hiratani)
所属:Department of Biochemistry and Molecular Biology&s_comma; SUNY Upstate Medical University&s_comma; NY&s_comma; USA

日時:11月10日(木)3時半--5時
場所:理学部2号館、201号

要旨:高等生物の発生過程において、DNA複製時期と遺伝子発現の調節とに相関があるとされている。しかしながら、DNA複製時期調節機構の実体あるいは遺伝子発現との相関の基盤はほぼ未解明と言ってよい。何故か。それはDNA複製時期の変化を目の当たりに観察する系が存在しないからである。我々は最近、マウスES細胞神経分化の系を用いてDNA複製時期のダイナミックな変化を観察することに初めて成功した。現在この系を用いてDNA複製時期調節の実体に迫りつつある。

参考文献:Hiratani&s_comma; I.&s_comma; Leskovar&s_comma; A.&s_comma; and Gilbert&s_comma; D. M. (2004).
Differentiation-induced replication-timing changes are restricted to AT-rich/long interspersed nuclear element (LINE)-rich isochores. Proc Natl Acad Sci U S A 101&s_comma;†16861-16866.

より詳しくは:
It is generally presumed that replication early in S-phase is a necessary (albeit not sufficient) condition for transcription&s_comma; whereas late-replicating sequences are assembled into transcriptionally inactive chromatin. Thus&s_comma; it was expected that some genes that change their transcription state during cellular differentiation were subject to replication timing changes&s_comma; and indeed we have recently identified many such genes within AT/LINE-rich isochores using a neural differentiation system of mouse embryonic stem (ES) cells (Hiratani et al.&s_comma; 2004&s_comma; PNAS 101:16861).
Here&s_comma; to gain a better understanding of the molecular events surrounding replication timing changes as they occur&s_comma; we have employed a more sophisticated&s_comma; highly homogeneous differentiation system of mouse ES cells (Rathjen et al.&s_comma; 2002&s_comma; Development 129:2649) that recapitulates neurectoderm differentiation in vivo. During a 9-day differentiation to neurectoderm&s_comma; ES-specific genes tested that switch their replication timing from early to late did so in between days 3 and 6&s_comma; in close relation with down-regulation of these genes. Interestingly&s_comma; this is coincident with the loss of pluripotence of ES cells that occurs in between days 5 and 6. On the other hand&s_comma; neurectoderm-specific genes tested that switch from late- to early-replication did so in between days 6 and 9&s_comma; when they become transcriptionally activated and the conversion of definitive ectoderm to neurectoderm occurs. From these observations&s_comma; it is interesting to speculate a close relation between replication timing regulation and cell fate decisions. As studies on a few anectodal genes imply that replication timing switches are regulated at the level of large chromosomal domains&s_comma; our current focus is on a chromosomal region surrounding a neurectoderm-specific gene&s_comma; Pleiotrophin (Ptn)&s_comma; which switches from late to early-replication upon neural differentiation. We have so far identified a 0.5 Mb region surrounding Ptn as the switching domain. Moreover&s_comma; we have observed a remarkable domain-wide transcriptional up-regulation within this 0.5 Mb domain upon differentiation. Because this up-regulation was observed regardless of the sequences being annotated&s_comma; these transcripts could represent non-coding or regulatory RNAs. Hence&s_comma; we seek to further define the nature of these transcripts and their possible link to replication timing changes.


:=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=< :=<
Masanori Taira&s_comma; Ph.D.
Laboratory of Molecular Biology&s_comma; Department of Biological Sciences Graduate School of Science&s_comma; University of Tokyo Building 2&s_comma; Room 065 7-3-1 Hongo&s_comma; Bunkyo-ku&s_comma; Tokyo 113-8654&s_comma; Japan Phone/FAX: Japan (81) 3-5841-4434
http://xextdb.nibb.ac.jp/

(The following is written in Japanese)
平良 眞規
東京大学 大学院理学系研究科 生物科学専攻 分子生物学研究室
理学部2号館、65号室、113-0033 東京都文京区本郷 7-3-1
電話/FAX:03-5841-4434; 学内から:24434
http://www.biol.s.u-tokyo.ac.jp/users/lmb/lmb-hp.html
http://xextdb.nibb.ac.jp/



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