Methylome profiling of healthy and central precocious puberty girls.
Methylome profiling of healthy and central precocious puberty girls.
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DOI：
10.1186/s13148-018-0581-1
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发表时间：
2018-11-22
影响因子：
5.7
通讯作者：
Latronico AC
中科院分区：
文献类型：
--
作者：
Bessa DS;Maschietto M;Aylwin CF;Canton APM;Brito VN;Macedo DB;Cunha-Silva M;Palhares HMC;de Resende EAMR;Borges MF;Mendonca BB;Netchine I;Krepischi ACV;Lomniczi A;Ojeda SR;Latronico AC
最近的研究表明，DNA甲基化（DNAm）的变化和两个印记基因（MKRN 3和DLK 1）的失活改变了女性青春期的开始。我们的目的是调查DNA谱与人类青春期的时间的关联分析外周血白细胞的全基因组DNA谱从10名女性中枢性性早熟（CPP）和33名健康女孩（15个前和18个后青春期）。为此，我们进行了组间比较：青春期前与青春期后，CPP与青春期前，CPP与青春期后。分析与正常青春期相关的甲基化组变化，我们在比较青春期前和青春期后健康女孩时确定了120个差异甲基化区域（DMR）。大多数这些DMR在青春期组（99%）和位于X染色体（74%）的高甲基化。只有一个基因组区域，包含ZFP 57的启动子，在青春期组中低甲基化。ZFP 57是一个转录抑制因子，它是多个基因组位点甲基化和印记所必需的。雌性恒河猴下丘脑中ZFP 57的表达在青春期发育期间增加，表明下游ZFP 57靶基因的抑制增强。其他14个锌指基因与正常青春期DMR的高甲基化有关。分析与CPP相关的甲基化组变化，我们证明与青春期前（81%）和青春期（89%）对照相比，CPP患者表现出更多的高甲基化CpG位点。48个ZNF基因被鉴定为在CPP中具有高甲基化的CpG位点。正常和性早熟女孩的甲基化组分析揭示了广泛的DNA超甲基化模式，表明人类的青春期过程与表观遗传驱动的调控控制的特定变化相关。此外，几个ZNF基因甲基化的变化似乎是一个独特的表观遗传修饰的基础上启动人类青春期。本文的在线版本（10.1186/s13148-018-0581-1）包含补充材料，可供授权用户使用。
Recent studies demonstrated that changes in DNA methylation (DNAm) and inactivation of two imprinted genes (MKRN3 and DLK1) alter the onset of female puberty. We aimed to investigate the association of DNAm profiling with the timing of human puberty analyzing the genome-wide DNAm patterns of peripheral blood leukocytes from ten female patients with central precocious puberty (CPP) and 33 healthy girls (15 pre- and 18 post-pubertal). For this purpose, we performed comparisons between the groups: pre- versus post-pubertal, CPP versus pre-pubertal, and CPP versus post-pubertal. Analyzing the methylome changes associated with normal puberty, we identified 120 differentially methylated regions (DMRs) when comparing pre- and post-pubertal healthy girls. Most of these DMRs were hypermethylated in the pubertal group (99%) and located on the X chromosome (74%). Only one genomic region, containing the promoter of ZFP57, was hypomethylated in the pubertal group. ZFP57 is a transcriptional repressor required for both methylation and imprinting of multiple genomic loci. ZFP57 expression in the hypothalamus of female rhesus monkeys increased during peripubertal development, suggesting enhanced repression of downstream ZFP57 target genes. Fourteen other zinc finger (ZNF) genes were related to the hypermethylated DMRs at normal puberty. Analyzing the methylome changes associated with CPP, we demonstrated that the patients with CPP exhibited more hypermethylated CpG sites compared to both pre-pubertal (81%) and pubertal (89%) controls. Forty-eight ZNF genes were identified as having hypermethylated CpG sites in CPP. Methylome profiling of girls at normal and precocious puberty revealed a widespread pattern of DNA hypermethylation, indicating that the pubertal process in humans is associated with specific changes in epigenetically driven regulatory control. Moreover, changes in methylation of several ZNF genes appear to be a distinct epigenetic modification underlying the initiation of human puberty. The online version of this article (10.1186/s13148-018-0581-1) contains supplementary material, which is available to authorized users.
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影响因子：
5.8
作者：
de Vries, L;Kauschansky, A;Phillip, M
通讯作者：
Phillip, M
由印记基因MKRN3突变引起的中央早熟青春期。
DOI：
10.1056/nejmoa1302160
发表时间：
2013-06-27
期刊：
The New England journal of medicine
影响因子：
--
作者：
Abreu AP;Dauber A;Macedo DB;Noel SD;Brito VN;Gill JC;Cukier P;Thompson IR;Navarro VM;Gagliardi PC;Rodrigues T;Kochi C;Longui CA;Beckers D;de Zegher F;Montenegro LR;Mendonca BB;Carroll RS;Hirschhorn JN;Latronico AC;Kaiser UB
通讯作者：
Kaiser UB
影响因子：
5.8
作者：
Brito, VN;Latronico, AC;Mendonca, BB
通讯作者：
Mendonca, BB
影响因子：
4.4
作者：
Grosso, S;Anichini, C;Morgese, G
通讯作者：
Morgese, G
影响因子：
9.8
作者：
Giorda, Roberto;Bonaglia, M. Clara;Zuffardi, Orsetta
通讯作者：
Zuffardi, Orsetta