Research progress of CCCTC-binding factor in central nervous system diseases

doi:10.3969/j.issn.1673-8640.2026.01.017

Abstract

Abstract:

CCCTC-binding factor （CTCF） is a ubiquitous transcription factor expressed in organisms，containing a special 11-zinc finger structure that can bind to DNA sequences or proteins，and participates in the regulation of gene expression. As a central regulator of chromatin topology，CTCF is involved in regulating neuronal cell differentiation，neuroinflammation and synaptic function，and is related to Alzheimer's disease（AD），Parkinson's disease（PD）and glioma. This review focuses on the role of CTCF in central nervous system diseases，in order to understand the pathogenesis of central nervous system diseases and provide potential clinical therapeutic targets.

Key words: CCCTC-binding factor, Alzheimer's disease, Parkinson's disease, Glioma

CLC Number:

R446.1

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.

Figures/Tables 1

References 49

[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