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      細(xì)胞重編程過程中核小體定位改變研究進(jìn)展

      2022-03-26 06:03:40崔浩亮史佩華高錦春張新博趙順然陶晨雨
      遺傳 2022年3期
      關(guān)鍵詞:能性染色質(zhì)重塑

      崔浩亮,史佩華,高錦春,張新博,趙順然,陶晨雨

      綜 述

      細(xì)胞重編程過程中核小體定位改變研究進(jìn)展

      崔浩亮,史佩華,高錦春,張新博,趙順然,陶晨雨

      河北農(nóng)業(yè)大學(xué)動物科技學(xué)院,保定 07100

      細(xì)胞重編程是指在精卵結(jié)合或核移植過程中,核遺傳物質(zhì)的表觀遺傳標(biāo)記發(fā)生刪除和重塑,從而使已分化的細(xì)胞成為具有全能性的過程。發(fā)生細(xì)胞重編程的方法主要有細(xì)胞融合、體細(xì)胞核移植以及誘導(dǎo)多能干細(xì)胞等。核小體是染色質(zhì)的基本結(jié)構(gòu)及功能單位,是染色質(zhì)的一級結(jié)構(gòu),核小體定位對基因的表達(dá)及細(xì)胞的狀態(tài)有著重要的調(diào)控作用。細(xì)胞重編程過程中核小體的含量和位置也會發(fā)生劇烈的變化,同時(shí)在相關(guān)基因啟動子位置的核小體含量也會降低從而促進(jìn)多能性基因的表達(dá)。本文綜述了核小體定位在基因激活與抑制、染色質(zhì)重塑以及轉(zhuǎn)錄因子識別中的作用,旨在為深入解析細(xì)胞重編程機(jī)制提供重要依據(jù)。

      細(xì)胞重編程;核小體定位;染色質(zhì)重塑;轉(zhuǎn)錄起始位點(diǎn)

      細(xì)胞重編程(cellular reprogramming)是指已經(jīng)分化的細(xì)胞在一些特殊條件下重新恢復(fù)到分化前的全能性狀態(tài)的過程,此過程包括多潛能基因的活躍表達(dá)、表觀遺傳標(biāo)記改變、核小體定位變化以及染色質(zhì)重塑等。實(shí)現(xiàn)細(xì)胞重編程的方法包括體細(xì)胞核移植、細(xì)胞融合以及誘導(dǎo)多能干細(xì)胞等,細(xì)胞重編程在醫(yī)學(xué)領(lǐng)域以及干細(xì)胞研究領(lǐng)域具有巨大應(yīng)用前景。但目前人們對重編程作用機(jī)制尚不清楚,同時(shí)細(xì)胞重編程效率低下極大限制了重編程的研究,因此探明重編程機(jī)制對當(dāng)前動物遺傳育種與繁殖研究具有重大意義。

      核小體的動態(tài)變化是基因組調(diào)節(jié)生物活動基礎(chǔ)特征之一,核小體定位在調(diào)節(jié)核小體結(jié)構(gòu)和功能方面發(fā)揮重要作用。有研究表明,在真核生物中大約75%~90%的基因組被包裝成核小體[1],細(xì)胞重編程過程中核小體定位發(fā)生明顯變化,且核小體分布呈現(xiàn)不均勻性,許多轉(zhuǎn)錄因子結(jié)合位點(diǎn)及轉(zhuǎn)錄起始位點(diǎn)存在明顯的核小體缺失區(qū)域[2]。核小體定位的改變是基因表達(dá)調(diào)控的重要方式之一,在細(xì)胞重編程過程中的核小體定位模式是目前研究熱點(diǎn)之一。

      1 細(xì)胞重編程過程中核小體定位

      1.1 細(xì)胞重編程過程中核小體覆蓋率變化

      已分化細(xì)胞可以通過核移植、細(xì)胞融合以及誘導(dǎo)多能干細(xì)胞(induced pluripotent stem cell, iPSC)技術(shù)重編程回到多能性細(xì)胞狀態(tài)[3](圖1)。向小鼠胚胎成纖維細(xì)胞(mouse embryonic fibroblasts, MEF)添加4種轉(zhuǎn)錄因子(OCT4、SOX2、KLF4和C-MYC),可以將MEF重編程為誘導(dǎo)多能干細(xì)胞及其前體細(xì)胞(pre-iPSC)。iPSC是一種研究細(xì)胞重編程的重要材料[4],核小體是染色質(zhì)的基本結(jié)構(gòu)單位,是基因表達(dá)的重要調(diào)節(jié)因子。iPSC的核小體定位模式與胚胎干細(xì)胞(embryonic stem cell, ESC)極其相似,而與MEF存在很大差別。DNA序列核小體覆蓋率一般通過與DNA序列結(jié)合的核小體數(shù)量表示。Huang等[5]分別比較了MEF、pre-iPSC和iPSC的全基因組核小體覆蓋率情況,從MEF到pre-iPSC,只有17.32%的基因組顯示較高的核小體覆蓋率,52.71%的基因組顯示較低核小體覆蓋率,這表明細(xì)胞重編程過程染色質(zhì)結(jié)構(gòu)傾向開放狀態(tài)。然而pre-iPSC進(jìn)一步誘導(dǎo)成iPSC,近50%的基因組區(qū)域傾向于獲得核小體,同時(shí)基因的開放程度降低,為解釋這一現(xiàn)象,該研究通過利用核小體二元體周圍標(biāo)簽位置的標(biāo)準(zhǔn)偏差計(jì)算核小體模糊度,發(fā)現(xiàn)pre-iPSC的核小體平均模糊度(26 bp)遠(yuǎn)低于MEF(31 bp)和iPSC(32 bp)的核小體模糊度,表明在pre-iPSC表現(xiàn)出更緊密的核小體定位,在完成重編程的iPSC中恢復(fù)為稀松的核小體定位模式。Tao等[6]通過體細(xì)胞核移植(somatic cell nuclear transplantation, SCNT)構(gòu)建豬()早期胚胎細(xì)胞,并對1000個(gè)受精卵(fertilized zygote, FZ)進(jìn)行了微球菌核酸酶測序(MNase-seq),相比發(fā)現(xiàn),由SCNT構(gòu)建的胚胎細(xì)胞整體核小體覆蓋率下降,編碼區(qū)的核小體覆蓋率由豬胚胎成纖維細(xì)胞(pig embryonic fibroblasts, PEF)的29.58%上升到31.97% (SCNT)、30.31% (FZ),而啟動子區(qū)的核小體覆蓋率從PEF的1.42%減少到SCNT的1.37%和FZ的1.3%,這種核小體定位階段性變化可能是為了胚胎階段的大規(guī)模轉(zhuǎn)錄做準(zhǔn)備。在細(xì)胞重編程過程中,轉(zhuǎn)錄因子結(jié)合位點(diǎn)以及轉(zhuǎn)錄起始位點(diǎn)核小體含量變低,這可能導(dǎo)致某些基因的表達(dá)量上升從而促進(jìn)細(xì)胞重編程的進(jìn)行。Jose等[7]將OCT4和KLF4轉(zhuǎn)導(dǎo)到腦源性神經(jīng)干細(xì)胞(neural stem cell, NSC)中,發(fā)現(xiàn)NSC比MEF更容易被誘導(dǎo)成iPSC,而且這一過程不需要外源SOX2或C-MYC[8]。這可能說明相比于核小體覆蓋率高的體細(xì)胞,具有較低核小體覆蓋率的干細(xì)胞更有利于細(xì)胞重編程發(fā)生[9]??傊?,核小體定位變化是細(xì)胞重編程的重要標(biāo)志之一。

      圖1 細(xì)胞重編程方法

      A:在體細(xì)胞培養(yǎng)過程中,通過添加4種轉(zhuǎn)錄因子,誘導(dǎo)重編程發(fā)生,使其轉(zhuǎn)變成誘導(dǎo)多能性細(xì)胞;B:通過將體細(xì)胞核移植到去核卵母細(xì)胞中,誘導(dǎo)細(xì)胞重編程,使其形成新的胚胎個(gè)體;C:通過細(xì)胞融合使體細(xì)胞來源的細(xì)胞核發(fā)生重編程。根據(jù)參考文獻(xiàn)[3]總結(jié)繪制。

      1.2 細(xì)胞重編程中轉(zhuǎn)錄起始位點(diǎn)核小體排布變化

      在探究核小體定位是如何影響細(xì)胞重編程過程中,發(fā)現(xiàn)在轉(zhuǎn)錄起始位點(diǎn)(turn start site, TSS)存在特定的核小體規(guī)范排列(–1, NDR (nucleosome deletion region), +1, +2……),這對基因表達(dá)起到至關(guān)重要的作用[10]。Tao等[11]通過利用3種體細(xì)胞重編程誘導(dǎo)成iPSC,發(fā)現(xiàn)iPSC的核小體定位模式與ESC幾乎相同,同時(shí)在活性基因TSS周圍有典型的核小體(–1、NDR、+1、+2、+3……)排布。而在小鼠() ESC和MEF中,高表達(dá)的基因比低表達(dá)的基因TSS周圍有更明顯的NDR[12]。類似的,在iPSC中多能性基因具有較高的表達(dá)水平,基因表達(dá)水平高低與NDR數(shù)量呈正相關(guān)[5,12]。Tao等[6]比較了若干個(gè)多能性基因、成纖維細(xì)胞特異性基因以及管家基因TSS周圍核小體定位模式,發(fā)現(xiàn)所選多能性基因TSS周圍的核小體定位模式在PEF是典型的沉默基因,但在SCNT和FZ中是典型的活躍基因,而成纖維細(xì)胞特異性基因TSS周圍的核小體定位模式則正好相反。這可能說明多能性基因可能在重編程的早期階段表達(dá)或準(zhǔn)備高表達(dá)??傊?,比較PEF、SCNT和FZ,沉默基因依舊沉默,多潛能基因TSS周圍趨向更加開放的染色質(zhì)結(jié)構(gòu)(NDR),使其轉(zhuǎn)錄活性升高。CpG島區(qū)域通常被認(rèn)為是哺乳動物的基因啟動子標(biāo)志,啟動子可以根據(jù)CpG島數(shù)量分為High-CG啟動子和Low-CG啟動子[13]。Huang等[5]通過觀察重編程過程中High-CG啟動子和Low-CG啟動子的核小體定位模式與基因表達(dá)之間的關(guān)系,發(fā)現(xiàn)Low-CG啟動子處存在明顯的核小體占據(jù),類似于沉默基因的核小體占據(jù)模式。相比之下,High-CG啟動子在TSS處存在明顯NDR和側(cè)翼區(qū)域的核小體高度富集,類似于活性基因的模式。如圖2A所示,在重編程過程中,多能性基因TSS周圍的核小體占據(jù)模式類似活性基因,表現(xiàn)典型的核小體定位模式(–1、NDR、+1、+2……)。成纖維細(xì)胞特異性基因TSS周圍的核小體占據(jù)模式類似沉默基因,表現(xiàn)典型的核小體占據(jù)模式。雖然許多因素都可以參與基因表達(dá)的調(diào)控,但本課題組觀察到核小體定位與基因表達(dá)之間存在很強(qiáng)的相關(guān)性,表明基因表達(dá)調(diào)控的靈活性在一定程度上受到核小體調(diào)控的影響。

      2 轉(zhuǎn)錄因子特異性識別核小體并促進(jìn)細(xì)胞重編程

      轉(zhuǎn)錄因子結(jié)合位點(diǎn)具有獨(dú)特的核小體結(jié)構(gòu),它們在轉(zhuǎn)錄過程中受核小體定位模式的調(diào)控[11]。干細(xì)胞多能性、細(xì)胞分化和細(xì)胞重編程過程需要轉(zhuǎn)錄因子(transcription factors, TFs)參與進(jìn)行,在細(xì)胞重新編程過程中,TFs通過與核小體覆蓋的DNA結(jié)合,引起染色質(zhì)封閉區(qū)域結(jié)構(gòu)改變,從而啟動新的表達(dá)模式[14,15]。在細(xì)胞重編程中Foxa1、OCT4、Ascl1/ E12a、PU1和Cebpa顯示很高的核小體親和力[16]。Foxa1可以取代組蛋白連接體,促進(jìn)局部染色質(zhì)開放,從而有利于其他轉(zhuǎn)錄因子與基因結(jié)合。Ebf1可以與致密染色質(zhì)結(jié)合,并誘導(dǎo)染色質(zhì)重塑[17,18]。SOX2是胚胎干細(xì)胞多能性的重要先導(dǎo)因子,SOX2可以在超螺旋位置結(jié)合并局部扭曲DNA,這有助于核小體組織與核小體末端DNA分離,從而增加DNA可及性[19]。與之相似,Michael等[20]發(fā)現(xiàn)OCT4與SOX2會不同程度地扭曲核小體結(jié)合的DNA,促進(jìn)DNA從組蛋白H2A和H3上脫離。OCT4、SOX2和KLF4能夠靶向優(yōu)先結(jié)合復(fù)合核小體的沉默位點(diǎn),從而激活基因[19,21],同時(shí)在另一個(gè)轉(zhuǎn)錄因子C-MYC的共同參與下,OCT4、SOX2和KLF4在重新編程的最初48小時(shí)與封閉染色質(zhì)緊密結(jié)合[22]。Run等[23]發(fā)現(xiàn)先鋒轉(zhuǎn)錄因子Leafy與核小體結(jié)合并與包括AP1在內(nèi)的大多數(shù)靶基因結(jié)合,隨后取代連接組蛋白H1并募集Swi/Snf,在局部“解鎖”染色質(zhì)。相似的,Gata3與染色質(zhì)結(jié)合,促使局部染色質(zhì)發(fā)生重塑以及提高增強(qiáng)子結(jié)合能力[24]。此外,在細(xì)胞重編程過程中,孤核受體Essrb可以募集轉(zhuǎn)錄因子OCT4、SOX2和NANOG進(jìn)入封閉染色質(zhì)區(qū)域,與包含穩(wěn)定核小體組織及高甲基化的DNA的增強(qiáng)子結(jié)合。如圖2B所示,這些結(jié)果說明TFs可以特異性識別重編程重要基因,雖然這些基因在已分化細(xì)胞中屬于核小體高覆蓋的沉默基因,但TFs可以識別核小體并促使核小體組織與DNA分離,以及驅(qū)動局部染色質(zhì)重構(gòu)促進(jìn)核小體重塑以及隨后的轉(zhuǎn)錄。

      圖2 細(xì)胞重編程中多能性基因及轉(zhuǎn)錄因子變化

      A:細(xì)胞重編程過程中多能性基因轉(zhuǎn)錄起始位點(diǎn)發(fā)生核小體缺失;B:轉(zhuǎn)錄因子結(jié)合靶核小體并改變?nèi)旧|(zhì)結(jié)構(gòu),從而刺激轉(zhuǎn)錄。

      3 核小體定位變化促進(jìn)染色質(zhì)重塑

      染色質(zhì)重塑是細(xì)胞重編程的重要標(biāo)志之一[25],染色質(zhì)/核小體重塑因子是利用ATP水解產(chǎn)生的能量來移動和調(diào)整核小體,從而調(diào)控DNA功能(轉(zhuǎn)錄、復(fù)制和DNA修復(fù))[26](圖3)。染色質(zhì)重塑因子可以分為4個(gè)家族:Swi/Snf (switch/sucrose non fermentable) 家族、Iswi (imitation switch)家族、Ino80 (inositol requiring 80)家族以及Chd (chromo helicase domain)家族。最初的重塑復(fù)合物是在酵母()中發(fā)現(xiàn)的Swi/Snf復(fù)合物[27]。這些重塑因子可以協(xié)同驅(qū)逐啟動子處核小體,從而創(chuàng)造NDR以實(shí)現(xiàn)基因表達(dá)[28]。Nap111通過偶聯(lián)染色質(zhì)重塑復(fù)合物Swi/Snf和Ino80降低核小體覆蓋率,促進(jìn)ES細(xì)胞分化[29]。Asf1是一種組蛋白伴侶,在和突變的細(xì)胞內(nèi)染色質(zhì)重組程度顯著降低[30]??傊?,Swi/Snf家族通過核小體滑動和移除改變?nèi)旧|(zhì)狀態(tài),以此調(diào)節(jié)靶基因的激活和抑制[31]。染色質(zhì)重塑因子Ino80可維持胚胎干細(xì)胞的多能性以及調(diào)節(jié)體細(xì)胞重編程為多能細(xì)胞,Cao等[32]發(fā)現(xiàn)Ino80可以調(diào)節(jié)滋養(yǎng)外胚層上皮通透性以促進(jìn)豬胚泡發(fā)育。此外,Ino80還被證明通過影響組蛋白乙?;瘉砭S持代謝平衡,將其破壞有概率導(dǎo)致疾病發(fā)生[33]。染色質(zhì)可及性復(fù)合體(chromatin accessible complex, CHRAC)是一種典型的核小體滑動因子,由ATP酶ISWI、ACF1亞基和一對組蛋白樣蛋白CHRAC-14/16組成[34],能調(diào)節(jié)核小體定位,改變?nèi)旧|(zhì)的規(guī)則性和完整性。這可能有助于抑制性染色質(zhì)的形成。標(biāo)志性亞單位ACF1在胚胎發(fā)育過程中的表達(dá)受到限制,但在原始生殖細(xì)胞中的表達(dá)仍然很高[35]。核小體重塑和去乙?;?nucleosome remodeling and deacetyla-tion, NuRD)復(fù)合物[36]在基因表達(dá)調(diào)控和干細(xì)胞自我更新中起著重要作用。在小鼠胚胎干細(xì)胞(ESC)和神經(jīng)祖細(xì)胞(neural progenitor cell, NPCs)分化過程中中,NuRD的基因組靶點(diǎn)是動態(tài)變化的,大多數(shù)結(jié)合發(fā)生在細(xì)胞特異基因的啟動子和增強(qiáng)子上[37]。Maud等[38]發(fā)現(xiàn)在ES中,染色質(zhì)重塑因子Chd1、Chd2、Chd4、Chd6、Chd8、Chd9、Brg1以及Ep400靶向結(jié)合NDR邊緣核小體,從而調(diào)節(jié)ES轉(zhuǎn)錄程序。核小體定位是建立染色質(zhì)結(jié)構(gòu)的基礎(chǔ)。在體細(xì)胞中,iPS技術(shù)可以誘導(dǎo)沉默的X染色體重新活化。在小鼠細(xì)胞重編程過程中,全能性的獲得與X染色體重新激活之間有很強(qiáng)關(guān)聯(lián)性[39]。Tao等[6]在對豬卵母細(xì)胞進(jìn)行SCNT也發(fā)現(xiàn)相似結(jié)果,同時(shí)在SCNT前期核小體占有率降低也可能是為X染色質(zhì)活化做準(zhǔn)備。這些結(jié)果表明X染色體的活化可能對細(xì)胞重編程的發(fā)生起到積極作用。綜上所述,染色質(zhì)重塑對細(xì)胞重編程起著至關(guān)重要的作用,染色質(zhì)重塑因子通過介導(dǎo)核小體定位動態(tài)變化(滑動、去除、解離、重新組裝)來實(shí)現(xiàn)染色質(zhì)重塑,從而影響細(xì)胞重編程的發(fā)生。

      圖3 染色質(zhì)重塑過程中的核小體定位變化

      A:細(xì)胞重編程過程中染色質(zhì)重塑因子結(jié)合核小體,并促進(jìn)核小體滑動,暴露出DNA片段;B:靶標(biāo)核小體去除;C:DNA與核小體發(fā)生解離;D:核小體變體替換原有核小體,改變?nèi)旧|(zhì)結(jié)構(gòu)。

      4 組蛋白變體在細(xì)胞重編程中的作用

      核小體是由長度約147 bp的DNA片段以及4種組蛋白(H2A、H2B、H3和H4)構(gòu)成的八聚體共同組成。組蛋白變體是一類特殊的組蛋白,其與常規(guī)組蛋白相差一個(gè)到幾百個(gè)氨基酸,組蛋白變體在細(xì)胞重編程過程中具有重要作用。在SCNT過程前期連接組蛋白H1會和異染色質(zhì)蛋白1 (HP1)發(fā)生置換;隨后組蛋白變體H3.3 (一種與基因激活相關(guān)的組蛋白變體)會參與重編程過程。在ESC中,組蛋白變體H3.3促使基因啟動子處建立H3K27三甲基而在低表達(dá)發(fā)育基因中建立雙價(jià)染色質(zhì),從而使特定基因在分化過程中表達(dá)[40]。連接組蛋白H1促進(jìn)高階染色質(zhì)折疊,對哺乳動物的發(fā)育至關(guān)重要,在基因的高GC區(qū)域和活性啟動子中富含H3K4三甲基,缺乏H1d和H1c,這與特征序列特征相關(guān)[41]。成熟精子和卵子染色質(zhì)包裝存在很大差異,但這些差異在脊椎動物早期胚胎中通過染色質(zhì)重新編程得到協(xié)調(diào)[42]。在斑馬魚受精卵中,處于轉(zhuǎn)錄靜止的雌原核DNA甲基化模式被重編程以匹配雄原核。在精子發(fā)生過程中,通過體細(xì)胞組蛋白與睪丸特異性組蛋白變體的交換完成染色質(zhì)重構(gòu)[43]。和功能相同且在卵母細(xì)胞和受精卵中高度表達(dá)[44,45],研究表明,它們的表達(dá)水平會隨著分化程度升高而降低。變異體誘導(dǎo)開放的染色質(zhì)結(jié)構(gòu),并在染色體上均勻分布;同時(shí)這些組蛋白變體與4種轉(zhuǎn)錄因子OCT4、SOX2、KLF4和C-MYC (OSKM)共表達(dá)時(shí)會增強(qiáng)iPSC的誘導(dǎo)成功率[46]。組蛋白變體H2A.Z通常定位在TSS的兩側(cè),Bagchi等[47]發(fā)現(xiàn)H2A.Z在NDR兩側(cè)是其雙向轉(zhuǎn)錄的特異性標(biāo)志。在iPSC重編程過程中,H2A.Z傾向于整合到高轉(zhuǎn)錄活性基因的TSS中[48]。綜上所述,組蛋白變體作為一種特殊的組蛋白,它們通過與常規(guī)組蛋白發(fā)生調(diào)換從而實(shí)現(xiàn)核小體定位改變以及組蛋白翻譯后修飾影響染色質(zhì)重塑,此外在胚胎形成過程中通過使配子的表觀遺傳修飾趨向一致來調(diào)控早期胚胎重編程過程。

      5 結(jié)語與展望

      隨著現(xiàn)代生物技術(shù)的快速發(fā)展,人們通過體細(xì)胞核移植技術(shù)、細(xì)胞融合技術(shù)以及誘導(dǎo)多能干細(xì)胞技術(shù)實(shí)現(xiàn)了人為細(xì)胞重編程,通過對細(xì)胞重編程過程及其調(diào)控機(jī)制的研究,發(fā)現(xiàn)核小體定位動態(tài)變化在細(xì)胞重編程過程具有十分關(guān)鍵的作用。細(xì)胞重編程過程中會激活多能性基因以及沉默另外一些特異性基因,其中就需要基因啟動子可以實(shí)現(xiàn)“自動開關(guān)”,這一過程是通過啟動子TSS位置的核小體動態(tài)變化來實(shí)現(xiàn)的。除此之外,在細(xì)胞重編程過程中,一些特殊轉(zhuǎn)錄因子以及染色質(zhì)重塑因子可以特異性結(jié)合核小體以及改變核小體定位,從而達(dá)到激活某些特定基因的目的,促進(jìn)細(xì)胞重編程。同時(shí),一些染色質(zhì)重塑因子會引起組蛋白變體置換,改變核小體結(jié)構(gòu),從而促進(jìn)細(xì)胞重編程?,F(xiàn)如今全基因組測序技術(shù)和分析方法的飛速發(fā)展使得人們對核小體定位的調(diào)控機(jī)制有了更深的了解,有利于發(fā)現(xiàn)更多的基因功能和表觀遺傳修飾。此外,關(guān)于細(xì)胞重編程過程的研究主要集中于小鼠與大鼠()這些模型動物上,相比之下在其他大型哺乳動物如豬、牛()、馬()的研究很少,在未來畜牧領(lǐng)域的研究具有巨大的應(yīng)用前景。

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      Progress on the study of nucleosome reorganization during cellular reprogramming

      Haoliang Cui, Peihua Shi, Jinchun Gao, Xinbo Zhang, Shunran Zhao, Chenyu Tao

      Cellular reprogramming is the process during which epigenetic markers of nuclear genome are deleted and remodeled during sperm-egg binding or nuclear transplantation, thereby rendering differentiated cells totipotent. The main cellular reprogramming methods are cell fusion, somatic cell nuclear transplantation, and induced pluripotent stem cells. Nucleosomes are the basic structural and functional units of chromatin, and nucleosome localization has an important role in regulating gene expression and the state of the cell. The occupancy and location of nucleosomes also change dramatically during cellular reprogramming, while the occupancy of nucleosomes around the transcriptional start site also decreases to promote the expression of pluripotency genes. In this review, we summarize the role of nucleosome localization in gene activation and repression, chromatin remodeling, and transcription factor recognition, with the aim of providing an important basis for an in-depth analysis of cellular reprogramming mechanisms.

      cellular reprogramming; nucleosome localization; chromatin remodeling; transcription initiation sites

      2021-08-13;

      2022-01-07;

      2022-02-24

      國家自然科學(xué)基金項(xiàng)目(編號:31802063),河北省自然科學(xué)基金項(xiàng)目(編號:C2020204058)和河北農(nóng)業(yè)大學(xué)引進(jìn)人才科研專項(xiàng)(編號:ZD201718)資助 [Supported by the National Natural Science Foundation of China (No. 31802063), Natural Science Foundation of Hebei Province (No. C2020204058) and Scientific Research Foundation for the Introduction of Talent in Hebei Agricultural University (No. ZD201718)]

      崔浩亮,在讀碩士研究生,專業(yè)方向:動物遺傳育種與繁殖。E-mail: 1522942442@qq.com

      陶晨雨,副教授,碩士生導(dǎo)師,研究方向:動物遺傳育種與繁殖。E-mail: taochenyuty@163.com

      10.16288/j.yczz.21-299

      (責(zé)任編委: 趙建國)

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