2月28日,，國際頂級學(xué)術(shù)期刊Cell發(fā)表了東南大學(xué)生命科學(xué)研究院/“發(fā)育與疾病相關(guān)基因”教育部重點(diǎn)實(shí)驗(yàn)室萬亞坤課題組關(guān)于“A Role for the Nucleoporin Nup170p in Chromatin Structure and Gene Silencing”的研究成果（Cell, Volume 152, Issue 5, 28 February 2013, Pages 969-983）。該工作由加拿大阿爾伯塔大學(xué),、美國系統(tǒng)生物學(xué)研究所和東南大學(xué)聯(lián)合完成,，受到國家自然基金資助，萬亞坤為論文并列第一作者,。
端粒是真核生物染色體中基因調(diào)控的一個(gè)特殊的位點(diǎn),，位于端粒附近的基因其轉(zhuǎn)錄活性往往受到抑制。但是,，細(xì)胞如何精確地調(diào)控端粒末端基因轉(zhuǎn)錄沉默的作用機(jī)理尚不清楚。萬亞坤等應(yīng)用系統(tǒng)生物學(xué)手段分析,，發(fā)現(xiàn)核孔復(fù)合物Nup170的缺失能導(dǎo)致端粒位置效應(yīng)的消失,，Nup170與組蛋白泛素化、組蛋白乙?；?、染色質(zhì)重塑分子等眾多參與染色質(zhì)結(jié)構(gòu)的基因存在著遺傳互作，并發(fā)現(xiàn)其與染色質(zhì)重塑分子Sth1之間存在著物理相互作用,。研究人員還系統(tǒng)地繪制了Nup170在基因組的結(jié)合草圖,，發(fā)現(xiàn)了Nup170與亞端粒的結(jié)合依賴于端粒沉默信息分子Sir4途徑。
本研究采用系統(tǒng)生物學(xué)的研究手段,，首次揭示核孔復(fù)合物通過與染色質(zhì)重塑分子作用調(diào)控亞端粒區(qū)域染色質(zhì)的結(jié)構(gòu),，進(jìn)而對位于亞端粒區(qū)域的基因轉(zhuǎn)錄沉默起著重要的調(diào)控作用。解決了長期以來人們對核孔復(fù)合物調(diào)控亞端?；虺聊饔脵C(jī)制這一科學(xué)難題,。亞端粒區(qū)的基因轉(zhuǎn)錄沉默與細(xì)胞衰老、人類疾病密切相關(guān),。通過系統(tǒng)地研究核孔復(fù)合物對端粒附近基因轉(zhuǎn)錄沉默的作用機(jī)制,，將為探索細(xì)胞衰老及相關(guān)疾病提供科學(xué)依據(jù),。（生物谷Bioon.com）
DOI: 10.1016/j.cell.2013.01.049
A Role for the Nucleoporin Nup170p in Chromatin Structure and Gene Silencing
David W. Van de Vosse,Yakun Wan,Diego L. Lapetina,Wei-Ming Chen,Jung-Hsien Chiang,John D. Aitchison,Richard W. Wozniak
Highlights
Nup170p physically interacts with Sir4p, Rap1p, and the chromatin remodeler RSC
Nup170p binds and represses expression of subtelomeric and ribosomal protein genes
Nup170p and Sir4p bind cooperatively to subtelomeric DNA
Tethering of subtelomeric chromatin to the NE during G1 phase requires Nup170p
Summary
Embedded in the nuclear envelope, nuclear pore complexes (NPCs) not only regulate nuclear transport but also interface with transcriptionally active euchromatin, largely silenced heterochromatin, as well as the boundaries between these regions. It is unclear what functional role NPCs play in establishing or maintaining these distinct chromatin domains. We report that the yeast NPC protein Nup170p interacts with regions of the genome that contain ribosomal protein and subtelomeric genes, where it functions in nucleosome positioning and as a repressor of transcription. We show that the role of Nup170p in subtelomeric gene silencing is linked to its association with the RSC chromatin-remodeling complex and the silencing factor Sir4p, and that the binding of Nup170p and Sir4p to subtelomeric chromatin is cooperative and necessary for the association of telomeres with the nuclear envelope. Our results establish the NPC as an active participant in silencing and the formation of peripheral heterochromatin.
