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

doi:10.16288/j.yczz.21-132

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Hereditas(Beijing) ›› 2021, Vol. 43 ›› Issue (8): 775-791.doi: 10.16288/j.yczz.21-132

• Orginal Articles • Previous Articles Next Articles

Serial deletions of tandem reverse CTCF sites reveal balanced HOXD regulatory landscape of enhancers

Ling Wang(), Jinhuan Li, Haiyan Huang(), Qiang Wu()

Center for Comparative Biomedicine, Key laboratory of Systems Biomedicine (Ministry of Education), Institute of Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China

Received:2021-04-11 Revised:2021-05-12 Online:2021-08-20 Published:2021-06-30
Contact: Huang Haiyan,Wu Qiang E-mail:wanglingmail0613@163.com;hy_huang@sjtu.edu.cn;qwu123@gmail.com
Supported by:
Supported by the National Natural Science Foundation of China Nos(31800636);Supported by the National Natural Science Foundation of China Nos(31630039);Supported by the National Natural Science Foundation of China Nos(91940303);Science and Technology Commission of Shanghai Municipality No(19JC1412500)

Abstract

Abstract:

The genome architectural protein CTCF (CCCTC-binding factor) not only mediates long-distance chromatin interactions between distal enhancers and target promoters, but also functions as an important insulator-binding factor to block improper enhancer activation of non-target promoters, and is thus of great significance to transcriptional regulation of developmental genes. The Hox (Homeobox) gene family plays an important role in the development of the brain, bones, and limbs. The spatiotemporal colinear expression of the HOXD cluster along the proximal-distal axis of limbs is regulated by two clusters of enhancers known as super-enhancers located in the flanking regulatory regions. We focused on the HOXD cluster to explore the architectural role of CTCF in transcriptional regulation of developmental genes. The HOXD cluster contains 9 paralogous genes intermixed with a series of CBS (CTCF-binding site) elements. Using the CRISPR DNA-fragment editing system, we generated a series of single-cell HEK293T clones with deletion of increasing numbers of reverse CBS elements. RNA-seq experiments revealed decreased levels of HOXD gene expression. In addition, chromosome conformation capture experiments revealed increased long-distance chromatin interactions between HOXD and the upstream enhancer cluster and corresponding decreased interactions between HOXD and the downstream enhancer cluster. Thus, tandem reverse CTCF sites function as insulators to maintain HOXD regulatory balance between the upstream and downstream enhancer clusters. This study has interesting implications on the precise gene expression control of the Hox family during animal development.

Key words: HOXD gene cluster, CTCF site, balanced regulatory mechanism, enhancer, insulator

Ling Wang, Jinhuan Li, Haiyan Huang, Qiang Wu. Serial deletions of tandem reverse CTCF sites reveal balanced HOXD regulatory landscape of enhancers[J]. Hereditas(Beijing), 2021, 43(8): 775-791.

Figures/Tables 7

Fig. 1

Table 1

Primers used in this study"

类型	引物名称	序列(5′→3′)
PCR	a1F	TTCCAGCACCTCGGCTTTGTC
	a1R	CCCACTTTCCACCTCTGTCCTG
	b1F	GTCCGCCCGTGAGCTTCTGAA
	b1R1	CTCACAGCAGCCGAAACCG
	c1F	TGATGCAGCCTCTGTGACCG
	c1R	AGTTTTCCCGTGGCGTCTGA
	e1F	TTCCCTGTCCCAGCTTGATTTC
	e1R	TCAACAGTGAAGGGCGGTGC
	e2F	CAAGCCACTCTCCCGCCACTA
	e2R	TCGCTCTCGTCCTCTCTTGGG
	e2R1	GGCTCCTGCACTGAGACCACA
sgRNA	sgRNA a1F	ACCGCGAAGAGTGCGGGAGAACGG
	sgRNA a1R	AAACCCGTTCTCCCGCACTCTTCG
	sgRNA b1F	ACCGGGCGCATCAGGAATGTAAG
	sgRNA b1R	AAACCTTACATTCCTGATGCGCC
	sgRNA c1F	ACCGCAGGCGAAGTGCGGTTTCCA
	sgRNA c1R	AAACTGGAAACCGCACTTCGCCTG
	sgRNA e1F	ACCGAACTGTGCTCAAACGCTCTC
	sgRNA e1R	AAACGAGAGCGTTTGAGCACAGTT
	sgRNA e2F	ACCGGAGGCGCAAACAGCTGTTGT
	sgRNA e2R	AAACACAACAGCTGTTTGCGCCTC
Index	Island5-bioprimer	5′biotin-AAACACAAATGCATCAACCTG
	GT2-bioprimer	5′biotin-GAGCCAAACTGTACCCCTAGC
	HOXD9-bioprimer	5′biotin-ACCGACTAGTTCGCAGGCT
	Island5-P5	AATGATACGGCGACCACCGAGATCTACACTCTTTCCCTACACGACGCTCTTCCGATCTATGCATCTCATGAAGCTGGCATCT
	GT2-P5	AATGATACGGCGACCACCGAGATCTACACTCTTTCCCTACACGACGCTCTTCCGATCTGTAACTTTAGCTAAACCAAGGCCT
	HOXD9-P5	AATGATACGGCGACCACCGAGATCTACACTCTTTCCCTACACGACGCTCTTCCGATCTCTGCAGCCTCCACCATTG
	P7-index-1	CAAGCAGAAGACGGCATACGAGATCGAGTAATGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-2	CAAGCAGAAGACGGCATACGAGATTCTCCGGAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-3	CAAGCAGAAGACGGCATACGAGATAATGAGCGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-4	CAAGCAGAAGACGGCATACGAGATGGAATCTCGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-5	CAAGCAGAAGACGGCATACGAGATTTCTGAATGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-6	CAAGCAGAAGACGGCATACGAGATACGAATTCGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-7	CAAGCAGAAGACGGCATACGAGATAGCTTCAGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-8	CAAGCAGAAGACGGCATACGAGATGCGCATTAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-9	CAAGCAGAAGACGGCATACGAGATCATAGCCGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-10	CAAGCAGAAGACGGCATACGAGATTTCGCGGAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-11	CAAGCAGAAGACGGCATACGAGATGCGCGAGAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-12	CAAGCAGAAGACGGCATACGAGATCTATCGCTGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-13	CAAGCAGAAGACGGCATACGAGATAGAGTACTGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-14	CAAGCAGAAGACGGCATACGAGATGCTCCGTAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-15	CAAGCAGAAGACGGCATACGAGATCATGAGAGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-16	CAAGCAGAAGACGGCATACGAGATTGAATCGCGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-17	CAAGCAGAAGACGGCATACGAGATGTCTGACTGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-18	CAAGCAGAAGACGGCATACGAGATCTGAATGCGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-19	CAAGCAGAAGACGGCATACGAGATCGCTTCTGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-20	CAAGCAGAAGACGGCATACGAGATTCGCATGAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-21	CAAGCAGAAGACGGCATACGAGATAATAGCAGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-22	CAAGCAGAAGACGGCATACGAGATGTCGCGTAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-23	CAAGCAGAAGACGGCATACGAGATACGCGATAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-24	CAAGCAGAAGACGGCATACGAGATTGATCGATGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-25	CAAGCAGAAGACGGCATACGAGATCCGCATGAGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-26	CAAGCAGAAGACGGCATACGAGATCCACAATCGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT
	P7-index-27	CAAGCAGAAGACGGCATACGAGATGATGTTCGGTGACTGGAGTTCAGACGTGTGCTCTTCCGATCT

Table 1

Fig. 2

Fig. 3

Fig. 4

Fig. 5

Fig. 6

References 59

[1]	Wu Q, Liu PF, Wang LY. Many facades of CTCF unified by its coding for three-dimensional genome architecture. J Genet Genomics, 2020, 47(8):407-424. doi: 10.1016/j.jgg.2020.06.008
[2]	Guo Y, Monahan K, Wu HY, Gertz J, Varley KE, Li W, Myers RM, Maniatis T, Wu Q. CTCF/cohesin-mediated DNA looping is required for protocadherin alpha promoter choice. Proc Natl Acad Sci USA, 2012, 109(51):21081-21086. doi: 10.1073/pnas.1219280110
[3]	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
[4]	Zhai YN, Xu Q, Guo Y, Wu Q. Characterization of a cluster of CTCF-binding sites in a protocadherin regulatory region. Hereditas(Beijing), 2016, 38(4):323-336.
	翟亚男, 许泉, 郭亚, 吴强. 原钙粘蛋白基因簇调控区域中成簇的CTCF结合位点分析. 遗传, 2016, 38(4):323-336.
[5]	Yin M, Wang J, Wang M, Li X, Zhang M, Wu Q, Wang Y. Molecular mechanism of directional CTCF recognition of a diverse range of genomic sites. Cell Res, 2017, 27(11):1365-1377. doi: 10.1038/cr.2017.131
[6]	Guo Y, Wu Q. Inversion of CTCF binding sites by DNA fragment editing alters genome topology and enhancer/ promoter functions. Hereditas(Beijing), 2015, 37(10):1073-1074.
	郭亚, 吴强. 采用DNA片段编辑技术反转CTCF结合位点改变基因组拓扑结构和增强子与启动子功能. 遗传, 2015, 37(10):1073-1074.
[7]	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. pmid: 8649389
[8]	Chen HB, Tian Y, Shu WJ, Bo XC, Wang SQ. Comprehensive identification and annotation of cell type-specific and ubiquitous CTCF-binding sites in the human genome. PLoS One, 2012, 7(7):e41374. doi: 10.1371/journal.pone.0041374
[9]	Nasmyth K. Disseminating the genome: Joining, resolving, and separating sister chromatids during mitosis and meiosis. Annu Rev Genet, 2001, 35:673-745. pmid: 11700297
[10]	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
[11]	Lu YJ, Shou J, Jia ZL, Wu YH, Li JH, Guo Y, Wu Q. Genetic evidence for asymmetric blocking of higher-order chromatin structure by CTCF/cohesin. Protein Cell, 2019, 10(12):914-920. doi: 10.1007/s13238-019-00656-y
[12]	Zheng XF, Huang HY, Wu Q. Chromatin architectural protein CTCF regulates gene expression of the UGT1 cluster. Hereditas(Beijing), 2019, 41(6):509-523.
	郑晓飞, 黄海燕, 吴强. 染色质架构蛋白CTCF调控UGT1基因簇的表达. 遗传, 2019, 41(6):509-523.
[13]	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
[14]	Wu YH, Jia ZL, Ge X, Wu Q. Three-dimensional genome architectural CCCTC-binding factor makes choice in duplicated enhancers at Pcdhα locus. Sci China Life Sci, 2020, 63(6):835-844.
[15]	Dekker J, Mirny L. The 3D genome as moderator of chromosomal communication. Cell, 2016, 164(6):1110-1121. doi: S0092-8674(16)30073-3 pmid: 26967279
[16]	Nichols MH, Corces VG. A tethered-inchworm model of SMC DNA translocation. Nat Struct Mol Biol, 2018, 25(10):906-910. doi: 10.1038/s41594-018-0135-4
[17]	Wu Q, Jia ZL. Wiring the brain by clustered protocadherin neural codes. Neurosci Bull, 2021, 37(1):117-131. doi: 10.1007/s12264-020-00578-4
[18]	Lin SG, Ba ZQ, Alt FW, Zhang Y. RAG chromatin scanning during V(D)J recombination and chromatin loop extrusion are related processes. Adv Immunol, 2018, 139:93-135.
[19]	Chen L, Carico Z, Shih HY, Krangel MS. A discrete chromatin loop in the mouse Tcra-Tcrd locus shapes the TCRdelta and TCRalpha repertoires. Nat Immunol, 2015, 16(10):1085-1093. doi: 10.1038/ni.3232
[20]	Majumder K, Koues OI, Chan EAW, Kyle KE, Horowitz JE, Yang-Iott K, Bassing CH, Taniuchi I, Krangel MS, Oltz EM. Lineage-specific compaction of Tcrb requires a chromatin barrier to protect the function of a long-range tethering element. J Exp Med, 2015, 212(1):107-120.
[21]	Rodríguez-Carballo E, Lopez-Delisle L, Zhan Y, Fabre PJ, Beccari L, El-Idrissi I, Huynh THN, Ozadam H, Dekker J, Duboule D. The HoxD cluster is a dynamic and resilient TAD boundary controlling the segregation of antagonistic regulatory landscapes. Genes Dev, 2017, 31(22):2264-2281.
[22]	Rodríguez-Carballo E, Lopez-Delisle L, Yakushiji- Kaminatsui N, Ullate-Agote A, Duboule D. Impact of genome architecture on the functional activation and repression of Hox regulatory landscapes. BMC Biol, 2019, 17(1):55.
[23]	Rodríguez-Carballo E, Lopez-Delisle L, Willemin A, Beccari L, Gitto S, Mascrez B, Duboule D. Chromatin topology and the timing of enhancer function at the HoxD locus. Proc Natl Acad Sci USA, 2020, 117(49):31231-31241.
[24]	Jia ZL, Wu Q. Clustered protocadherins emerge as novel susceptibility loci for mental disorders. Front Neurosci, 2020, 14:587819. doi: 10.3389/fnins.2020.587819
[25]	Heger P, Marin B, Bartkuhn M, Schierenberg E, Wiehe T. The chromatin insulator CTCF and the emergence of metazoan diversity. Proc Natl Acad Sci USA, 2012, 109(43):17507-17512. doi: 10.1073/pnas.1111941109
[26]	Lewis EB. A gene complex controlling segmentation in Drosophila. Nature, 1978, 276(5688):565-570. doi: 10.1038/276565a0
[27]	Mallo M. Reassessing the role of Hox genes during vertebrate development and evolution. Trends Genet, 2018, 34(3):209-217.
[28]	Kmita M, Duboule D. Organizing axes in time and space; 25 years of colinear tinkering. Science, 2003, 301(5631):331-333. doi: 10.1126/science.1085753
[29]	Andrey G, Montavon T, Mascrez B, Gonzalez F, Noordermeer D, Leleu M, Trono D, Spitz F, Duboule D. A switch between topological domains underlies HoxD genes collinearity in mouse limbs. Science, 2013, 340(6137):1234167.
[30]	Beccari L, Yakushiji-Kaminatsui N, Woltering JM, Necsulea A, Lonfat N, Rodríguez-Carballo E, Mascrez B, Yamamoto S, Kuroiwa A, Duboule D. A role for Hox13 proteins in the regulatory switch between TADs at the HoxD locus. Genes Dev, 2016, 30(10):1172-1186.
[31]	Montavon T, Soshnikova N, Mascrez B, Joye E, Thevenet L, Splinter E, de Laat W, Spitz F, Duboule D. A regulatory archipelago controls Hox genes transcription in digits. Cell, 2011, 147(5):1132-1145.
[32]	Lonfat N, Montavon T, Darbellay F, Gitto S, Duboule D. Convergent evolution of complex regulatory landscapes and pleiotropy at Hox loci. Science, 2014, 346(6212):1004-1006.
[33]	Long HK, Prescott SL, Wysocka J. Ever-changing landscapes: Transcriptional enhancers in development and evolution. Cell, 2016, 167(5):1170-1187. doi: 10.1016/j.cell.2016.09.018
[34]	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
[35]	Kim S, Shendure J. Mechanisms of interplay between transcription factors and the 3D genome. Mol Cell, 2019, 76(2):306-319. doi: 10.1016/j.molcel.2019.08.010
[36]	Noordermeer D, Leleu M, Splinter E, Rougemont J, De Laat W, Duboule D. The dynamic architecture of Hox gene clusters. Science, 2011, 334(6053):222-225.
[37]	Li JH, Shou J, Guo Y, Tang YX, Wu YH, Jia ZL, Zhai YN, Chen ZF, Xu Q, Wu Q. Efficient inversions and duplications of mammalian regulatory DNA elements and gene clusters by CRISPR/Cas9. J Mol Cell Biol, 2015, 7(4):284-298. doi: 10.1093/jmcb/mjv016
[38]	Chang N, Sun C, Gao L, Zhu D, Xu X, Zhu X, Xiong JW, Xi JJ. Genome editing with RNA-guided Cas9 nuclease in zebrafish embryos. Cell Res, 2013, 23(4):465-472. doi: 10.1038/cr.2013.45
[39]	Doudna JA, Charpentier E. Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science, 2014, 346(6213):1258096. doi: 10.1126/science.1258096
[40]	Liu PF, Wu Q. Probing 3D genome by CRISPR/Cas9. Hereditas(Beijing), 2020, 42(1):18-31.
	刘沛峰, 吴强. CRISPR/Cas9基因编辑在三维基因组研究中的应用. 遗传, 2020, 42(1):18-31.
[41]	Li JH, Shou J, Wu Q. DNA fragment editing of genomes by CRISPR/Cas9. Hereditas(Beijing), 2015, 37(10):992-1002.
	李金环, 寿佳, 吴强. CRISPR/Cas9系统在基因组DNA片段编辑中的应用. 遗传, 2015, 37(10):992-1002.
[42]	Trapnell C, Roberts A, Goff L, Pertea G, Kim D, Kelley DR, Pimentel H, Salzberg SL, Rinn JL, Pachter L. Differential gene and transcript expression analysis of RNA-seq experiments with tophat and cufflinks. Nat Protoc, 2012, 7(3):562-578. doi: 10.1038/nprot.2012.016 pmid: 22383036
[43]	Guo XQ, Chen FZ, Gao F, Li L, Liu K, You LJ, Hua C, Yang F, Liu WL, Peng CH, Wang LN, Yang XX, Zhou FY, Tong JW, Cai J, Li ZY, Wan B, Zhang L, Yang T, Zhang MW, Yang LL, Yang YW, Zeng WJ, Wang B, Wei XF, Xu X. CNSA: A data repository for archiving omics data. Database (Oxford), 2020; 2020: baaa055.
[44]	Chen FZ, You LJ, Yang F, Wang LN, Guo XQ, Gao F, Hua C, Tan C, Fang L, Shan RQ, Zeng WJ, Wang B, Wang R, Xu X, Wei XF. CNGBdb: China National Genebank Database. Hereditas(Beijing), 2020, 42(08):799-809.
	陈凤珍, 游丽金, 杨帆, 王丽娜, 郭学芹, 高飞, 华聪, 谈聪, 方林, 单日强, 曾文君, 王博, 王韧, 徐讯, 魏晓锋. CNGBdb: 国家基因库生命大数据平台. 遗传, 2020, 42(8):799-809.
[45]	Pearson JC, Lemons D, McGinnis W. ModulatingHox gene functions during animal body patterning. Nat Rev Genet, 2005, 6(12):893-904. pmid: 16341070
[46]	Lonfat N, Duboule D. Structure, function and evolution of topologically associating domains (TADs) atHox loci. FEBS Lett, 2015, 589(20):2869-2876. doi: 10.1016/j.febslet.2015.04.024
[47]	Holland PW, Garcia-Fernàndez J, Williams NA, Sidow A. Gene duplications and the origins of vertebrate development. Dev Suppl, 1994, 125-133.
[48]	Shou J, Li J, Liu Y, Wu Q. Precise and predictable CRISPR chromosomal rearrangements reveal principles of Cas9-mediated nucleotide insertion. Mol Cell, 2018, 71(4):498-509 e4. doi: S1097-2765(18)30466-0 pmid: 30033371
[49]	Fu YF, Foden JA, Khayter C, Maeder ML, Reyon D, Joung JK, Sander JD. High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol, 2013, 31(9):822-826. doi: 10.1038/nbt.2623
[50]	Perry MW, Boettiger AN, Levine M. Multiple enhancers ensure precision of gap gene-expression patterns in the Drosophila embryo. Proc Natl Acad Sci USA, 2011, 108(33):13570-13575. doi: 10.1073/pnas.1109873108
[51]	Frankel N, Davis GK, Vargas D, Wang S, Payre F, Stern DL. Phenotypic robustness conferred by apparently redundant transcriptional enhancers. Nature, 2010, 466(7305):490-493. doi: 10.1038/nature09158
[52]	Barolo S. Shadow enhancers: Frequently asked questions about distributed cis-regulatory information and enhancer redundancy. Bioessays, 2012, 34(2):135-141. doi: 10.1002/bies.201100121 pmid: 22083793
[53]	Buecker C, Wysocka J. Enhancers as information integration hubs in development: Lessons from genomics. Trends Genet, 2012, 28(6):276-284. doi: 10.1016/j.tig.2012.02.008
[54]	Jolma A, Yin YM, Nitta KR, Dave K, Popov A, Taipale M, Enge M, Kivioja T, Morgunova E, Taipale J. DNA- dependent formation of transcription factor pairs alters their binding specificity. Nature, 2015, 527(7578):384-388. doi: 10.1038/nature15518
[55]	Wang N, Jia ZL, Wu Q. RFX5 regulates gene expression of the Pcdhα cluster.Hereditas(Beijing), 2020, 42(8):760-774. doi: 10.16288/j.yczz.20-184 pmid: 32952112
	王娜, 甲芝莲, 吴强. RFX5调控原钙粘蛋白α基因簇的表达. 遗传, 2020, 42(8):760-774. doi: 10.16288/j.yczz.20-184 pmid: 32952112
[56]	Malik S, Roeder RG. The metazoan mediator co-activator complex as an integrative hub for transcriptional regulation. Nat Rev Genet, 2010, 11(11):761-772.
[57]	Bolt CC, Duboule D. The regulatory landscapes of developmental genes. Development, 2020, 147(3): dev171736. doi: 10.1242/dev.171736
[58]	Neijts R, Deschamps J. At the base of colinearHox gene expression: Cis-features and trans-factors orchestrating the initial phase of Hox cluster activation. Dev Biol, 2017, 428(2):293-299. doi: S0012-1606(16)30864-8 pmid: 28728680
[59]	Xu DF, Ma RS, Zhang JH, Liu ZJ, Wu B, Peng JH, Zhai YN, Gong QG, Shi YY, Wu JH, Wu Q, Zhang ZY, Ruan K. Dynamic nature of CTCF tandem 11 zinc fingers in multivalent recognition of DNA as revealed by NMR spectroscopy. J Phys Chem Lett, 2018, 9(14):4020-4028. doi: 10.1021/acs.jpclett.8b01440

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Serial deletions of tandem reverse CTCF sites reveal balanced HOXD regulatory landscape of enhancers

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[12]	Changbin Sun, Xi Zhang. Advance in the research on super-enhancer [J]. Hereditas(Beijing), 2016, 38(12): 1056-1068.
[13]	FENG Jun LI Guang WANG Yi-Quan. Research progress of conserved non-coding elements in metazoan [J]. HEREDITAS, 2013, 35(1): 35-44.
[14]	GUO Xin-Jun. Properties comparing and evolutionary analysis of MEF2 of Homo sapiens based on bioinformatic methods [J]. HEREDITAS, 2011, 33(9): 975-981.
[15]	GAO Yun-Zhen, BO Yu-Chun. Progress of transcription factor CCAAT enhancer binding protein β [J]. HEREDITAS, 2011, 33(3): 198-206.