5-Formylcytosine landscapes of human preimplantation embryos at single-cell resolution

被引：11

作者：

Gao, Yun ^{[1
,2
]}

Li, Lin ^{[3
]}

Yuan, Peng ^{[1
,4
]}

Zhai, Fan ^{[1
,4
]}

Ren, Yixin ^{[1
,4
]}

Yan, Liying ^{[1
,4
,5
]}

Li, Rong ^{[1
,4
]}

Lian, Ying ^{[1
,4
]}

Zhu, Xiaohui ^{[1
,4
]}

Wu, Xinglong ^{[1
,2
,6
,7
]}

Kee, Kehkooi ^{[8
]}

Wen, Lu ^{[1
,2
]}

Qiao, Jie ^{[1
,4
,5
,6
]}

Tang, Fuchou ^{[1
,2
,6
]}

机构：

[1] Peking Univ, Hosp 3, Beijing Adv Innovat Ctr Genom, Sch Life Sci,Dept Obstet & Gynecol, Beijing, Peoples R China

[2] Peking Univ, Biomed Pioneering Innovaiton Ctr, Minist Educ, Key Lab Cell Proliferat & Differentiat, Beijing, Peoples R China

[3] Southern Med Univ, Sch Basic Med Sci, Dept Pathophysiol, Guangdong Prov Key Lab Prote, Guangzhou, Peoples R China

[4] Minist Educ, Key Lab Assisted Reprod, Beijing, Peoples R China

[5] Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China

[6] Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China

[7] Peking Univ, Acad Adv Interdisciplinary Studies, Beijing, Peoples R China

[8] Tsinghua Univ, Ctr Stem Cell Biol & Regenerat Med, Sch Med, Dept Basic Med Sci, Beijing, Peoples R China

来源：

PLOS BIOLOGY | 2020年 / 18卷 / 07期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

TET PROTEINS; DNA; BASE; 5-HYDROXYMETHYLCYTOSINE; 5-METHYLCYTOSINE; NUCLEOTIDE; CONVERSION; DYNAMICS; DEFECTS;

D O I：

10.1371/journal.pbio.3000799

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Epigenetic dynamics, such as DNA methylation and chromatin accessibility, have been extensively explored in human preimplantation embryos. However, the active demethylation process during this crucial period remains largely unexplored. In this study, we use single-cell chemical-labeling-enabled C-to-T conversion sequencing (CLEVER-seq) to quantify the DNA 5-formylcytosine (5fC) levels of human preimplantation embryos. We find that 5-formylcytosine phosphate guanine (5fCpG) exhibits genomic element-specific distribution features and is enriched in L1 and endogenous retrovirus-K (ERVK), the subfamilies of repeat elements long interspersed nuclear elements (LINEs) and long terminal repeats (LTRs), respectively. Unlike in mice, paired pronuclei in the same zygote present variable difference of 5fCpG levels, although the male pronuclei experience stronger global demethylation. The nucleosome-occupied regions show a higher 5fCpG level compared with nucleosome-depleted ones, suggesting the role of 5fC in organizing nucleosome position. Collectively, our work offers a valuable resource for ten-eleven translocation protein family (TET)-dependent active demethylation-related study during human early embryonic development.

引用

页数：23