检验医学 ›› 2026, Vol. 41 ›› Issue (1): 95-100.DOI: 10.3969/j.issn.1673-8640.2026.01.017
收稿日期:2024-09-14
修回日期:2025-02-05
出版日期:2026-01-30
发布日期:2026-01-30
通讯作者:
侯玉丽
作者简介:侯玉丽,E-mail:15810629076@163.com。基金资助:
GAO Shuo, WANG Peichang, HOU Yuli(
)
Received:2024-09-14
Revised:2025-02-05
Online:2026-01-30
Published:2026-01-30
Contact:
HOU Yuli
摘要:
CCCTC结合因子(CTCF)是一种在生物体中普遍表达的多功能转录因子,含有特殊的11-锌指结构,能够与DNA序列或蛋白质结合,参与基因的表达调控。CTCF作为染色质拓扑结构的中心调节因子,参与调节神经元细胞分化、神经炎症和突触功能,与阿尔茨海默病(AD)、帕金森病(PD)和神经胶质瘤密切相关。文章就CTCF在中枢神经系统疾病中的作用进行综述,以期了解中枢神经系统疾病的发病机制,提供潜在的临床治疗靶点。
中图分类号:
高硕, 王培昌, 侯玉丽. CCCTC结合因子在中枢神经系统疾病中的作用研究进展[J]. 检验医学, 2026, 41(1): 95-100.
GAO Shuo, WANG Peichang, HOU Yuli. Research progress of CCCTC-binding factor in central nervous system diseases[J]. Laboratory Medicine, 2026, 41(1): 95-100.
| [1] |
ZHANG C, YANG X, WAN D, et al. Burden of neurological disorders in China and its provinces,1990-2021:findings from the global burden of disease study 2021[J]. Med, 2025, 6(8):100692.
DOI URL |
| [2] |
BISSERIER M, MATHIYALAGAN P, ZHANG S, et al. Regulation of the methylation and expression levels of the BMPR2 gene by SIN3a as a novel therapeutic mechanism in pulmonary arterial hypertension[J]. Circulation, 2021, 144(1):52-73.
DOI PMID |
| [3] |
QIU Y, HUANG S. CTCF-mediated genome organization and leukemogenesis[J]. Leukemia, 2020, 34(9):2295-2304.
DOI PMID |
| [4] |
SEITAN V C, KRANGEL M S, MERKENSCHLAGER M. Cohesin, CTCF and lymphocyte antigen receptor locus rearrangement[J]. Trends Immunol, 2012, 33(4):153-159.
DOI PMID |
| [5] |
CIPRIANO A, MOQRI M, MAYBURY-LEWIS S Y, et al. Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming[J]. Nat Aging, 2024, 4(1):14-26.
DOI PMID |
| [6] |
DEHINGIA B, MILEWSKA M, JANOWSKI M, et al. CTCF shapes chromatin structure and gene expression in health and disease[J]. EMBO Rep, 2022, 23(9):e55146.
DOI URL |
| [7] |
MOHANA G, DORIER J, LI X, et al. Chromosome-level organization of the regulatory genome in the Drosophila nervous system[J]. Cell, 2023, 186(18):3826-3844.
DOI PMID |
| [8] |
MADABHUSHI R, GAO F, PFENNING A R, et al. Activity-induced DNA breaks govern the expression of neuronal early-response genes[J]. Cell, 2015, 161(7):1592-1605.
DOI PMID |
| [9] |
ZHANG J, HU G, LU Y, et al. CTCF mutation at R567 causes developmental disorders via 3D genome rearrangement and abnormal neurodevelopment[J]. Nat Commun, 2024, 15(1):5524.
DOI PMID |
| [10] |
HIRAYAMA T, TARUSAWA E, YOSHIMURA Y, et al. CTCF is required for neural development and stochastic expression of clustered Pcdh genes in neurons[J]. Cell Rep, 2012, 2(2):345-357.
DOI PMID |
| [11] |
ELBERT A, VOGT D, WATSON A, et al. CTCF governs the identity and migration of MGE-derived cortical interneurons[J]. J Neurosci, 2019, 39(1):177-192.
DOI PMID |
| [12] |
KIM S, YU N K, SHIM K W, et al. Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor(CTCF)[J]. J Neurosci, 2018, 38(22):5042-5052.
DOI URL |
| [13] |
MCGILL B E, BARVE R A, MALONEY S E, et al. Abnormal microglia and enhanced inflammation-related gene transcription in mice with conditional deletion of Ctcf in Camk2a-Cre-expressing neurons[J]. J Neurosci, 2018, 38(1):200-219.
DOI URL |
| [14] |
NARDINI N, CALIEBE A, NAGEL I, et al. CTCF variants in 39 individuals with a variable neurodevelopmental disorder broaden the mutational and clinical spectrum[J]. Genet Med, 2019, 21(12):2723-2733.
DOI PMID |
| [15] |
CHEN J, XIAO Y, LI D, et al. New insights into the mechanisms of high-fat diet mediated gut microbiota in chronic diseases[J]. Imeta, 2023, 2(1):e69.
DOI PMID |
| [16] |
徐勇, 王军, 王虹峥, 等. 2023中国阿尔茨海默病数据与防控策略[J]. 阿尔茨海默病及相关病杂志, 2023, 6(3):175-192.
DOI |
| [17] |
DUBOIS B, BURNIE N, BOZEAT S, et al. Biomarkers in Alzheimer's disease:role in early and differential diagnosis and recognition of atypical variants[J]. Alzheimers Res Ther, 2023, 15(1):175.
DOI |
| [18] |
HOU Y, SONG Q, GAO S, et al. CTCF mediates replicative senescence through POLD1[J]. Front Cell Dev Biol, 2021, 9:618586.
DOI URL |
| [19] |
SAMS D S, RAZ D, TAL M, et al. Neuronal CTCF is necessary for basal and experience-dependent gene regulation,memory formation,and genomic structure of BDNF and Arc[J]. Cell Rep, 2016, 17(9):2418-2430.
DOI URL |
| [20] |
VOSTROV A A, TAHENY M J, QUITSCHKE W W. A region to the N-terminal side of the CTCF zinc finger domain is essential for activating transcription from the amyloid precursor protein promoter[J]. J Biol Chem, 2002, 277(2):1619-1627.
DOI PMID |
| [21] |
GU H, LIU L L, WU A, et al. Lead acetate exposure and cerebral amyloid accumulation:mechanistic evaluations in APP/PS1 mice[J]. Environ Health Perspect, 2024, 132(10):107004.
DOI URL |
| [22] |
HUBER J, TANASIE N L, ZERNIA S, et al. Single-molecule imaging reveals a direct role of CTCF's zinc fingers in SA interaction and cluster-dependent RNA recruitment[J]. Nucleic Acids Res, 2024, 52(11):6490-6506.
DOI PMID |
| [23] | ZHOU X, ZHU Z, KUANG S, et al. Tetramethylpyrazine nitrone(TBN)reduces amyloid β deposition in Alzheimer's disease models by modulating APP expression,BACE1 activity,and autophagy pathways[J]. Pharmaceuticals(Basel), 2024, 17(8):1005. |
| [24] |
PATEL P J, REN Y, YAN Z. Epigenomic analysis of Alzheimer's disease brains reveals diminished CTCF binding on genes involved in synaptic organization[J]. Neurobiol Dis, 2023, 184:106192.
DOI URL |
| [25] |
SATO K, TAKAYAMA K I, HASHIMOTO M, et al. Transcriptional and post-transcriptional regulations of amyloid-β precursor protein(APP)mRNA[J]. Front Aging, 2021, 2:721579.
DOI URL |
| [26] |
LIU N, ZHANG T, ZHAO W, et al. Current trends in blood biomarkers detection and neuroimaging for Parkinson's disease[J]. Ageing Res Rev, 2025, 104:102658.
DOI URL |
| [27] |
IBANEZ L, DUBE U, SAEF B, et al. Parkinson disease polygenic risk score is associated with Parkinson disease status and age at onset but not with alpha-synuclein cerebrospinal fluid levels[J]. BMC Neurol, 2017, 17(1):198.
DOI PMID |
| [28] | 甄隽颖, 郑晓丹, 吴军. 人类诱导多能干细胞在帕金森病治疗中的研究进展[J]. 中风与神经疾病杂志, 2020, 37(1):84-86. |
| [29] |
TOLOSA E, GARRIDO A, SCHOLZ S W, et al. Challenges in the diagnosis of Parkinson's disease[J]. Lancet Neurol, 2021, 20(5):385-397.
DOI PMID |
| [30] |
FREEMAN D M, WANG Z. Epigenetic vulnerability of insulator CTCF motifs at Parkinson's disease-associated genes in response to neurotoxicant rotenone[J]. Front Genet, 2020, 11:627.
DOI PMID |
| [31] |
OH S, SHAO J, MITRA J, et al. Enhancer release and retargeting activates disease-susceptibility genes[J]. Nature, 2021, 595(7869):735-740.
DOI |
| [32] |
YOUNG T R, YAMAMOTO M, KIKUCHI S S, et al. Thalamocortical control of cell-type specificity drives circuits for processing whisker-related information in mouse barrel cortex[J]. Nat Commun, 2023, 14(1):6077.
DOI PMID |
| [33] | CHENG F, ZHENG W, LIU C, et al. Intronic enhancers of the human SNCA gene predominantly regulate its expression in brain in vivo[J]. Sci Adv, 2022, 8(47):eabq6324. |
| [34] |
OSTROM Q T, CIOFFI G, WAITE K, et al. CBTRUS statistical report:primary brain and other central nervous system tumors diagnosed in the United States in 2014-2018[J]. Neuro Oncol, 2021, 23(12Suppl 2): iii1-iii105.
DOI URL |
| [35] |
方丹东, 程岗, 黄伟, 等. 脑胶质瘤组织lncRNA SOX21-AS1、miR-875-5p表达及其与患者预后的关系[J]. 检验医学, 2024, 39(3):209-214.
DOI |
| [36] |
OHGAKI H, KLEIHUES P. Genetic pathways to primary and secondary glioblastoma[J]. Am J Pathol, 2007, 170(5):1445-1453.
DOI PMID |
| [37] |
ZHAN Z, LIU Z, GAO H, et al. Anticancer effects of OSW-1 on glioma cells via regulation of the PI3K/AKT signal pathway:a network pharmacology approach and experimental validation in vitro and in vivo[J]. Front Pharmacol, 2022, 13:967141.
DOI URL |
| [38] |
MAMIVAND A, BAYAT S, MAGHROUNI A, et al. Data mining of bulk and single-cell RNA sequencing introduces OBI1-AS1 as an astrocyte marker with possible role in glioma recurrence and progression[J]. Clin Epigenetics, 2022, 14(1):35.
DOI PMID |
| [39] |
GHIMIRE P, KAMALUDIN A, PALAU B F, et al. MGMT methylation and its prognostic significance in inoperable IDH-wildtype glioblastoma:the MGMT-GBM study[J]. Acta Neurochir(Wien), 2024, 166(1):394.
DOI |
| [40] |
MONTEAGUDO-SÁNCHEZ A, RICHARD ALBERT J, SCARPA M, et al. The impact of the embryonic DNA methylation program on CTCF-mediated genome regulation[J]. Nucleic Acids Res, 2024, 52(18):10934-10950.
DOI URL |
| [41] |
ARUTLA V, BACOLOD M D, WANG W, et al. Genomic space of MGMT in human glioma revisited:novel motifs,regulatory RNAs,NRF1,2,and CTCF involvement in gene expression[J]. Int J Mol Sci, 2021, 22(5):2492.
DOI URL |
| [42] |
FLAVAHAN W A, DRIER Y, LIAU B B, et al. Insulator dysfunction and oncogene activation in IDH mutant gliomas[J]. Nature, 2016, 529(7584):110-114.
DOI |
| [43] |
RAHME G J, JAVED N M, XIN S, et al. Modeling epigenetic lesions that cause gliomas[J]. Cell, 2023, 186(17):3674-3685.
DOI PMID |
| [44] |
LIU C, NAGASHIMA H, FERNANDO N, et al. A CTCF-binding site in the Mdm1-Il22-Ifng locus shapes cytokine expression profiles and plays a critical role in early Th1 cell fate specification[J]. Immunity, 2024, 57(5):1005-1018.e7.
DOI PMID |
| [45] | 亓合媛, 李艳明, 熊倩, 等. CTCF通过ALAS2调控K562细胞红系分化[J]. 发育医学电子杂志, 2017, 5(1):1-7. |
| [46] |
ORESKOVIC E, WHEELER E C, MENGWASSER K E, et al. Genetic analysis of cancer drivers reveals cohesin and CTCF as suppressors of PD-L1[J]. Proc Natl Acad Sci U S A, 2022, 119(7):e2120540119.
DOI URL |
| [47] | SHI Y, WU L, YU X, et al. Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)[J]. Cancer Commun(Lond), 2022, 42(12):1314-1330. |
| [48] |
NISHIMURA W, IWASA H, TUMURKHUU M. Role of the transcription factor MAFA in the maintenance of pancreatic β-cells[J]. Int J Mol Sci, 2022, 23(9):4478.
DOI URL |
| [49] |
WANG R R, QIU X, PAN R, et al. Dietary intervention preserves β cell function in mice through CTCF-mediated transcriptional reprogramming[J]. J Exp Med, 2022, 219(7):e20211779.
DOI URL |
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