The ICF syndrome protein CDCA7 harbors a unique DNA binding domain that recognizes a CpG dyad in the context of a non-B DNA

作者全名："Hardikar, Swanand; Ren, Ren; Ying, Zhengzhou; Zhou, Jujun; Horton, John R.; Bramble, Matthew D.; Liu, Bin; Lu, Yue; Liu, Bigang; Della Coletta, Luis; Shen, Jianjun; Dan, Jiameng; Zhang, Xing; Cheng, Xiaodong; Chen, Taiping"

作者地址："[Hardikar, Swanand; Ren, Ren; Ying, Zhengzhou; Zhou, Jujun; Horton, John R.; Bramble, Matthew D.; Liu, Bin; Lu, Yue; Liu, Bigang; Della Coletta, Luis; Shen, Jianjun; Dan, Jiameng; Zhang, Xing; Cheng, Xiaodong; Chen, Taiping] Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Houston, TX 77030 USA; [Liu, Bin; Cheng, Xiaodong; Chen, Taiping] Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci, Program Genet & Epigenet, Houston, TX 77030 USA; [Ying, Zhengzhou] chongqing Med Univ, Coll Lab Med, Key Lab Lab Med Diagnost, Minist Educ, Chongqing 400016, Peoples R China; [Dan, Jiameng] Kunming Univ Sci & technol, Inst Primate Translat Med, State Key Lab Primate Biomed Res, Kunming 650500, Yunnan, Peoples R China"

通信作者："Cheng, XD; Chen, TP (通讯作者)，Univ Texas MD Anderson Canc Ctr, Dept Epigenet & Mol Carcinogenesis, Houston, TX 77030 USA.; Cheng, XD; Chen, TP (通讯作者)，Univ Texas MD Anderson Canc Ctr, UTHlth Grad Sch Biomed Sci, Program Genet & Epigenet, Houston, TX 77030 USA."

来源：SCIENCE ADVANCES

ESI学科分类：Multidisciplinary

WOS号：WOS:001297874700008

JCR分区：Q1

影响因子：13.6

年份：2024

卷号：10

期号：34

开始页：　

结束页：　

文献类型：Article

关键词：　

摘要："CDCA7, encoding a protein with a carboxyl-terminal cysteine-rich domain (CRD), is mutated in immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, a disease related to hypomethylation of juxtacentromeric satellite DNA. How CDCA7 directs DNA methylation to juxtacentromeric regions is unknown. Here, we show that the CDCA7 CRD adopts a unique zinc-binding structure that recognizes a CpG dyad in a non-B DNA formed by two sequence motifs. CDCA7, but not ICF mutants, preferentially binds the non-B DNA with strand-specific CpG hemi-methylation. The unmethylated sequence motif is highly enriched at centromeres of human chromosomes, whereas the methylated motif is distributed throughout the genome. At S phase, CDCA7, but not ICF mutants, is concentrated in constitutive heterochromatin foci, and the formation of such foci can be inhibited by exogenous hemi-methylated non-B DNA bound by the CRD. Binding of the non-B DNA formed in juxtacentromeric regions during DNA replication provides a mechanism by which CDCA7 controls the specificity of DNA methylation."

基金机构："National Institutes of Health [R01AI1214030, R35GM134744]; Cancer Prevention and Research Institute of Texas [RR160029]; Sam and Freda Davis Fund Fellowship; Cockrell Family Foundation in Houston; National Institutes of Health Equipment [S10_RR25528, S10_RR028976, S10_OD027000]; U.S. Department of Energy [W-31-109-Eng-38]; National Synchrotron Light Source II resources [17-ID-1, DE-SC0012704]"

基金资助正文："this work was financially supported by the National Institutes of Health grant R01AI1214030 (t.c.), National Institutes of Health grant R35GM134744 (X.c.), Cancer Prevention and Research Institute of Texas grant RR160029 (X.c.), Sam and Freda Davis Fund Fellowship (Z.Y.), the Cockrell Family Foundation in Houston (J.Z.), National Institutes of Health Equipment grants S10_RR25528, S10_RR028976, and S10_OD027000, U.S. Department of Energy contract W-31-109-Eng-38, and National Synchrotron Light Source II resources 17-ID-1 under contract DE-SC0012704."