CTCF在介导三维基因组形成及调控基因表达中的研究进展

doi:10.16288/j.yczz.21-326

遗传 ›› 2021, Vol. 43 ›› Issue (9): 816-821.doi: 10.16288/j.yczz.21-326

CTCF在介导三维基因组形成及调控基因表达中的研究进展

周聪(), 周强伟, 成盛, 李国亮()

华中农业大学信息学院,农业生物信息学湖北省重点实验室,农业大数据湖北省工程技术研究中心,三维基因组学研究中心,武汉 430070

收稿日期:2021-09-08 修回日期:2021-09-13 出版日期:2021-09-20 发布日期:2021-09-15
通讯作者: 李国亮 E-mail:zhoucong@mail.hzau.edu.cn;guoliang.li@mail.hzau.edu.cn
作者简介:周聪,博士,在站博士后,研究方向：三维基因组学。E-mail: zhoucong@mail.hzau.edu.cn
基金资助:
国家自然科学基金项目资助编号(31970590);国家自然科学基金项目资助编号(31771402)

Research progress of CTCF in mediating 3D genome formation and regulating gene expression

Cong Zhou(), Qiangwei Zhou, Sheng Cheng, Guoliang Li()

Agricultural Bioinformatics Key Laboratory of Hubei Province, Hubei Engineering Technology Research Center of Agricultural Big Data, 3D Genomics Research Center, College of Informatics, Huazhong Agricultural University, Wuhan 430070, China

Received:2021-09-08 Revised:2021-09-13 Online:2021-09-20 Published:2021-09-15
Contact: Li Guoliang E-mail:zhoucong@mail.hzau.edu.cn;guoliang.li@mail.hzau.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China Nos(31970590);Supported by the National Natural Science Foundation of China Nos(31771402)

摘要/Abstract

摘要：

真核细胞间期的染色质在细胞核中经过复杂的盘曲折叠,形成高级拓扑结构,这样的染色质结构空间组织对基因表达有重要影响。CTCF (CCCTC-binding factor)作为关键的染色质高级结构架构蛋白,对三维基因组结构的形成起到了重要作用。CTCF还可以与基因组内大量的绝缘子结合,影响染色质远程交互,实现对增强子和基因转录调控的绝缘效应。本文主要对近期美国圣裘德儿童研究医院Chunliang Li团队对于CTCF完全降解后发现染色质可及性发生变化的研究结果,上海交通大学系统生物医学研究院吴强团队、美国加州路德维希癌症研究所任兵团队对于CTCF结合位点充当绝缘子作用机制的最新结果进行部分点评及讨论。

关键词: CTCF, 绝缘子, 三维基因组, 基因表达调控

Abstract:

In interphase eukaryotic nuclei, chromatin is folded to form a higher-order topological structure. The spatial organization of such chromatin domain has an important impact on the regulation of gene expression. As a key architectural structural protein, CTCF (CCCTC-binding factor) plays an important role in the formation of chromatin three-dimensional chromatin structure. CTCF can also bind to many insulator elements in the genome and insulate enhancers from activating target genes via modulating remote chromatin interactions. A recent study by Dr. Chunliang Li and his team at St. Jude Children’s Research Hospital in the United States showed that when CTCF was acutely degraded, significant changes were found in the three-dimensional structure of chromatin. The mechanism by which CTCF binding sites function as insulator elements was investigated by Prof. Qiang Wu’s team at Institute of Systems Biomedicine and Shanghai Jiao Tong University in China and Prof. Bing Ren’s team at Ludwig Institute for Cancer Research in the United States. Here we mainly review and discuss some of these latest progresses.

Key words: CTCF, insulator, three-dimensional genome, regulation of gene expression

周聪, 周强伟, 成盛, 李国亮. CTCF在介导三维基因组形成及调控基因表达中的研究进展[J]. 遗传, 2021, 43(9): 816-821.

Cong Zhou, Qiangwei Zhou, Sheng Cheng, Guoliang Li. Research progress of CTCF in mediating 3D genome formation and regulating gene expression[J]. Hereditas(Beijing), 2021, 43(9): 816-821.

图/表 1

参考文献 26

[1]	Schmitt AD, Hu M, Ren B. Genome-wide mapping and analysis of chromosome architecture. Nat Rev Mol Cell Biol, 2016, 17(12):743-755. doi: 10.1038/nrm.2016.104
[2]	Schoenfelder S, Fraser P. Long-range enhancer-promoter contacts in gene expression control. Nat Rev Genet, 2019, 20(8):437-455. doi: 10.1038/s41576-019-0128-0 pmid: 31086298
[3]	Zheng H, Xie W. The role of 3D genome organization in development and cell differentiation. Nat Rev Mol Cell Biol, 2019, 20(9):535-550. doi: 10.1038/s41580-019-0132-4
[4]	Niu LJ, Shen W, Shi ZY, Tan YJ, He N, Wan J, Sun JL, Zhang YD, Huang YZ, Wang WJ, Fang C, Li JS, Zheng PP, Cheung E, Chen YL, Li L, Hou CH. Three-dimensional folding dynamics of the Xenopus tropicalis genome. Nat Genet, 2021, 53(7):1075-1087. doi: 10.1038/s41588-021-00878-z
[5]	Sanborn AL, Rao SSP, Huang SC, Durand NC, Huntley MH, Jewett AI, Bochkov ID, Chinnappan D, Cutkosky A, Li J, Geeting KP, Gnirke A, Melnikov A, McKenna D, Stamenova EK, Lander ES, Aiden EL. Chromatin extrusion explains key features of loop and domain formation in wild-type and engineered genomes. Proc Natl Acad Sci USA, 2015, 112(47):E6456-6465. doi: 10.1073/pnas.1518552112
[6]	Guo Y, Xu Q, Canzio D, Shou J, Li JH, Gorkin DU, Jung I, Wu HY, Zhai YN, Tang YX, Lu YC, Wu YH, Jia ZL, Li W, Zhang MQ, Ren B, Krainer AR, Maniatis T, Wu Q. CRISPR inversion of CTCF sites alters genome topology and enhancer/promoter function. Cell, 2015, 162(4):900-910. doi: 10.1016/j.cell.2015.07.038 pmid: 26276636
[7]	Kim Y, Shi ZB, Zhang HS, Finkelstein IJ, Yu HT. Human cohesin compacts DNA by loop extrusion. Science, 2019, 366(6471):1345-1349. doi: 10.1126/science.aaz4475
[8]	Handoko L, Xu H, Li GL, Ngan CY, Chew E, Schnapp M, Lee CWH, Ye CP, Ping JLH, Mulawadi F, Wong E, Sheng JP, Zhang YB, Poh T, Chan CS, Kunarso G, Shahab A, Bourque G, Cacheux-Rataboul V, Sung WK, Ruan YJ, Wei CL. CTCF-mediated functional chromatin interactome in pluripotent cells. Nat Genet, 2011, 43(7):630-638. doi: 10.1038/ng.857 pmid: 21685913
[9]	Phillips JE, Corces VG. CTCF: master weaver of the genome. Cell, 2009, 137(7):1194-1211. doi: 10.1016/j.cell.2009.06.001
[10]	Huang H, Zhu Q, Jussila A, Han YY, Bintu B, Kern C, Conte M, Zhang YX, Bianco S, Chiariello AM, Yu M, Hu R, Tastemel M, Juric I, Hu M, Nicodemi M, Zhuang XW, Ren B. CTCF mediates dosage- and sequence-context- dependent transcriptional insulation by forming local chromatin domains. Nat Genet, 2021, 53(7):1064-1074. doi: 10.1038/s41588-021-00863-6
[11]	Filippova GN, Fagerlie S, Klenova EM, Myers C, Dehner Y, Goodwin G, Neiman PE, Collins SJ, Lobanenkov VV. An exceptionally conserved transcriptional repressor, CTCF, employs different combinations of zinc fingers to bind diverged promoter sequences of avian and mammalian c-myc oncogenes. Mol Cell Biol, 1996, 16(6):2802-2813. doi: 10.1128/MCB.16.6.2802 pmid: 8649389
[12]	Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R, Santos-Simarro F, Gilbert-Dussardier B, Wittler L, Borschiwer M, Haas SA, Osterwalder M, Franke M, Timmermann B, Hecht J, Spielmann M, Visel A, Mundlos S. Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions. Cell, 2015, 161(5):1012-1025. doi: S0092-8674(15)00377-3 pmid: 25959774
[13]	Shukla S, Kavak E, Gregory M, Imashimizu M, Shutinoski B, Kashlev M, Oberdoerffer P, Sandberg R, Oberdoerffer S. CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing. Nature, 2011, 479(7371):74-79. doi: 10.1038/nature10442
[14]	Vostrov AA, Quitschke WW. The zinc finger protein CTCF binds to the APBbeta domain of the amyloid beta-protein precursor promoter. Evidence for a role in transcriptional activation. J Biol Chem, 1997, 272(52):33353-33359. pmid: 9407128
[15]	Zhang XF, Zhang Y, Ba ZQ, Kyritsis N, Casellas R, Alt FW. Fundamental roles of chromatin loop extrusion in antibody class switching. Nature, 2019, 575(7782):385-389. doi: 10.1038/s41586-019-1723-0
[16]	Bell AC, Felsenfeld G. Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene. Nature, 2000, 405(6785):482-485. doi: 10.1038/35013100
[17]	Lobanenkov VV, Nicolas RH, Adler VV, Paterson H, Klenova EM, Polotskaja AV, Goodwin GH. A novel sequence-specific DNA binding protein which interacts with three regularly spaced direct repeats of the CCCTC-motif in the 5'-flanking sequence of the chicken c-myc gene. Oncogene, 1990, 5(12):1743-1753. pmid: 2284094
[18]	Jia ZL, Li JW, Ge X, Wu YH, Guo Y, Wu Q. Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection. Genome Biol, 2020, 21(1):75. doi: 10.1186/s13059-020-01984-7
[19]	Tang ZH, Luo OJ, Li XW, Zheng MZ, Zhu JJ, Szalaj P, Trzaskoma P, Magalska A, Wlodarczyk J, Ruszczycki B, Michalski P, Piecuch E, Wang P, Wang DJ, Tian SZ, Penrad-Mobayed M, Sachs LM, Ruan XA, Wei CL, Liu ET, Wilczynski GM, Plewczynski D, Li GL, Ruan YJ. CTCF-mediated human 3D genome architecture reveals chromatin topology for transcription. Cell, 2015, 163(7):1611-1627. doi: 10.1016/j.cell.2015.11.024
[20]	Hyle J, Zhang Y, Wright S, Xu BS, Shao Y, Easton J, Tian LQ, Feng RP, Xu P, Li CL. Acute depletion of CTCF directly affects MYC regulation through loss of enhancer- promoter looping. Nucleic Acids Res, 2019, 47(13):6699-6713. doi: 10.1093/nar/gkz462
[21]	Nora EP, Goloborodko A, Valton AL, Gibcus JH, Uebersohn A, Abdennur N, Dekker J, Mirny LA, Bruneau BG. Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell, 2017, 169(5): 930-944.e22. doi: 10.1016/j.cell.2017.05.004
[22]	Xu BS, Wang H, Wright S, Hyle J, Zhang Y, Shao Y, Niu MM, Fan YP, Rosikiewicz W, Djekidel MN, Peng JM, Lu R, Li CL. Acute depletion of CTCF rewires genome-wide chromatin accessibility. Genome Biol, 2021, 22(1):244. doi: 10.1186/s13059-021-02466-0
[23]	Kemp CJ, Moore JM, Moser R, Bernard B, Teater M, Smith LE, Rabaia NA, Gurley KE, Guinney J, Busch SE, Shaknovich R, Lobanenkov VV, Liggitt D, Shmulevich I, Melnick A, Filippova GN. CTCF haploinsufficiency destabilizes DNA methylation and predisposes to cancer. Cell Rep, 2014, 7(4):1020-1029. doi: 10.1016/j.celrep.2014.04.004
[24]	West AG, Gaszner M, Felsenfeld G. Insulators: many functions, many mechanisms. Genes Dev, 2002, 16(3):271-288. doi: 10.1101/gad.954702
[25]	Wang L, Li JH, Huang HY, Wu Q. Serial deletions of tandem reverse CTCF sites reveal balanced HOXD regulatory landscape of enhancers. Hereditas(Beijing), 2021, 43(8):775-791.
	王玲, 李金环, 黄海燕, 吴强. 串联反向CTCF位点的系列删除揭示增强子调控HOXD基因簇表达的平衡. 遗传, 2021, 43(8):775-791.
[26]	He XL, Li JH, Wu Q. Combinatorial CRISPR inversions of CTCF sites in HOXD cluster reveal complex insulator function. Hereditas(Beijing), 2021, 43(8):758-774.
	何象龙, 李金环, 吴强. HOXD基因簇内一系列CTCF位点反转揭示绝缘子功能. 遗传, 2021, 43(8):758-774.

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CTCF在介导三维基因组形成及调控基因表达中的研究进展

Research progress of CTCF in mediating 3D genome formation and regulating gene expression

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