Oncotarget

Research Papers: Pathology:

Genome-wide 5-hydroxymethylcytosine modification pattern is a novel epigenetic feature of globozoospermia

Xiu-Xia Wang, Bao-Fa Sun, Jiao Jiao, Ze-Chen Chong, Yu-Shen Chen, Xiao-Li Wang, Yue Zhao, Yi-Ming Zhou and Da Li _

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Oncotarget. 2015; 6:6535-6543. https://doi.org/10.18632/oncotarget.3163

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Abstract

Xiu-Xia Wang1, Bao-Fa Sun2, Jiao Jiao1, Ze-Chen Chong2, Yu-Shen Chen2, Xiao-Li Wang2, Yue Zhao3, Yi-Ming Zhou4, Da Li1

1Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang 110004, China

2Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing 101300, China

3Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang 110001, China

4Department of Medicine, Brigham and Women’s Hospital, Harvard Institutes of Medicine, Harvard Medical School, Boston, MA 02115, USA

Correspondence to:

Da Li, e-mail: leeda@ymail.com

Keywords: 5-hydroxymethylcytosine, epigenetic, genomic imprinting, globozoospermia

Received: December 23, 2014     Accepted: January 17, 2015     Published: February 02, 2015

ABSTRACT

Discovery of 5-hydroxymethylcytosine (5hmC) in mammalian genomes has excited the field of epigenetics, but information on the genome-wide distribution of 5hmC is limited. Globozoospermia is a rare but severe cause of male infertility. To date, the epigenetic mechanism, especially 5hmC profiles involved in globozoospermia progression, remains largely unknown. Here, utilizing the chemical labeling and biotin-enrichment approach followed by Illumina HiSeq sequencing, we showed that (i) 6664, 9029 and 6318 genes contain 5hmC in normal, abnormal, and globozoospermia sperm, respectively; (ii) some 5hmC-containing genes significantly involves in spermatogenesis, sperm motility and morphology, and gamete generation; (iii) 5hmC is exclusively localized in sperm intron; (iv) approximately 40% imprinted genes have 5hmC modification in sperm genomes, but globozoospermia sperm exhibiting a large portion of imprinted genes lose the 5hmC modification; (v) six imprinted genes showed different 5hmC patterns in abnormal sperm (GDAP1L1, GNAS, KCNK9, LIN28B, RB1, RTL1), and five imprinted genes showed different 5hmC patterns in globozoospermia sperm (KCNK9, LIN28B, RB1, SLC22A18, ZDBF2). These results suggested that differences in genome-wide 5hmC patterns may in part be responsible for the sperm phenotype. All of this may improve our understanding of the basic molecular mechanism underlying sperm biology and the etiology of male infertility.


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