Position-dependent correlation between TBX22 exon 5 methylation and palatal shelf fusion in the development of cleft palate

被引:2
作者
Li, Ke [1 ]
Shu, Xuan [1 ]
Gong, Hui [2 ]
Cheng, Liuhanghang [1 ]
Dong, Zejun [1 ]
Shu, Shenyou [1 ]
机构
[1] Shantou Univ, Med Coll, Affiliated Hosp 2, Cleft Lip & Palate Treatment Ctr, 69 Dongxia North Rd, Jinping Dist 515041, Shantou, Peoples R China
[2] Shantou Univ, Med Coll, Affiliated Hosp 2, Dept Gynaecol, 69 Dongxia North Rd, Jinping Dist 515041, Shantou, Peoples R China
来源
ANAIS DA ACADEMIA BRASILEIRA DE CIENCIAS | 2019年 / 91卷 / 02期
基金
美国国家科学基金会;
关键词
DNA methylation; cleft palate; TBX22; CpG site; DNA-METHYLATION; MOLECULAR-MECHANISMS; EXPRESSION ANALYSIS; FREQUENT CAUSE; MUTATIONS; PATTERNS; GENETICS; PROMOTER; REVEALS; GENES;
D O I
10.1590/0001-3765201920180945
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
DNA methylation is essential for spatiotemporally-regulated gene expression in embryonic development. TBX22 (Chr X: 107667964-107688978) functioning as a transcriptional repressor affects DNA binding, sumoylation, and transcriptional repression associated with X-linked cleft palate. This study aimed to explore the relationship and potential mechanism between TBX22 exon 5 methylation and palatal shelf fusion induced by all-trans retinoic acid (ATRA). We performed DNA methylation profiling, using MethylRAD-seq, after high throughput sequencing of mouse embryos from control (n=9) and ATRA-treated (to induce cleft palate, n=9) C57BL/6J mice at embryonic gestation days(E) 13.5, 14.5 and 16.5. TBX22 exon 5 was hyper-methylated at the CpG site at E13.5 (P=0.025, log2FC=1.5) and E14.5 (P=0.011, log2FC: 1.5) in ATRA-treated, whereas methylation TBX22 exon 5 at the CpG site was not significantly different at E16.5 (P=0.808, log2FC=-0.2) between control and ATRA-treated. MSP results showed a similar trend consistent with the MethylRAD-seq results. qPCR showed the change in TBX22 exon 5 expression level negatively correlated with its TBX22 exon 5 methylation level. These results indicate that changes in TBX22 exon 5 methylation might play an important regulatory role during palatal shelf fusion, and may enlighten the development of novel epigenetic biomarkers in the treatment of CP in the future.
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页数:9
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