Activation-Induced Cytidine Deaminase Induces DNA Demethylation of Pluripotency Genes in Bovine Differentiated Cells

被引:4
作者
Moon, Song-Yi [1 ]
Eun, Hye-Ju [1 ]
Baek, Sang-Ki [1 ]
Jin, Sang-Jin [1 ]
Kim, Tae-Suk [1 ,2 ]
Kim, Sung-Woo [3 ]
Seong, Hwan-Hoo [3 ]
Choi, In-Chul [4 ]
Lee, Joon-Hee [1 ,2 ]
机构
[1] Gyeongsang Natl Univ, Dept Anim Biosci, Coll Agr & Life Sci, Jinju 52828, South Korea
[2] Gyeongsang Natl Univ, Inst Agr & Life Sci, Coll Agr & Life Sci, Jinju, South Korea
[3] Natl Inst Anim Sci, Rural Dev Adm, Anim Genet Resources Stn, Namwon, South Korea
[4] Chungnam Natl Univ, Coll Agr & Life Sci, Div Anim & Dairy Sci, Daejeon, South Korea
基金
新加坡国家研究基金会;
关键词
BASE EXCISION-REPAIR; SINGLE-STRANDED-DNA; STEM-CELLS; MAMMALIAN DEVELOPMENT; NUCLEAR TRANSFER; PATERNAL GENOME; METHYLATION; AID; 5-METHYLCYTOSINE; 5-HYDROXYMETHYLCYTOSINE;
D O I
10.1089/cell.2015.0076
中图分类号
Q813 [细胞工程];
学科分类号
摘要
Activation-induced cytidine deaminase (AID) is the only enzyme that has been suggested as a putative DNA demethylase in mammals. However, very little is known about AID function as DNA demethylase of bovine differentiated cells toward pluripotent state. To investigate the effect of AID on DNA demethylation, bovine AID complementary DNAs were transfected into bovine differentiated cells, which were mostly methylated in the promoter regions of pluripotency genes. As a result, AID-transfected bovine cells started to transform into colonies at day 19 of transfection. The colonies derived from the transfected cells showed positive alkaline phosphatase (AP) staining and expression of pluripotency genes (OCT-3/4, NANOG, SOX2) and pluripotency-related antigens (SSEA-4, TRA1-60, TRA1-81), which have been widely used to characterize human embryonic stem cells. In particular, the levels of OCT-3/4 and NANOG expression were significantly increased in the AID-transfected cells when compared with the control and empty vector-transfected cells (p < 0.05). Finally, DNA demethylation in the promoter regions of pluripotency genes (OCT-3/4, NANOG) was significantly increased compared with the control (p < 0.05). These results demonstrate that the induction of the AID gene into bovine differentiated cells improves DNA demethylation and expression of pluripotency genes.
引用
收藏
页码:298 / 308
页数:11
相关论文
共 41 条
[1]   A mammalian protein with specific demethylase activity for mCpG DNA [J].
Bhattacharya, SK ;
Ramchandani, S ;
Cervoni, N ;
Szyf, M .
NATURE, 1999, 397 (6720) :579-583
[2]   A critical role for AID in the initiation of reprogramming to induced pluripotent stem cells [J].
Bhutani, Nidhi ;
Decker, Matthew N. ;
Brady, Jennifer J. ;
Bussat, Rose T. ;
Burns, David M. ;
Corbel, Stephane Y. ;
Blau, Helen M. .
FASEB JOURNAL, 2013, 27 (03) :1107-1113
[3]   DNA Demethylation Dynamics [J].
Bhutani, Nidhi ;
Burns, David M. ;
Blau, Helen M. .
CELL, 2011, 146 (06) :866-872
[4]   Reprogramming towards pluripotency requires AID-dependent DNA demethylation [J].
Bhutani, Nidhi ;
Brady, Jennifer J. ;
Damian, Mara ;
Sacco, Alessandra ;
Corbel, Stephane Y. ;
Blau, Helen M. .
NATURE, 2010, 463 (7284) :1042-U57
[5]   THE ESSENTIALS OF DNA METHYLATION [J].
BIRD, A .
CELL, 1992, 70 (01) :5-8
[6]   Uncovering the role of 5-hydroxymethylcytosine in the epigenome [J].
Branco, Miguel R. ;
Ficz, Gabriella ;
Reik, Wolf .
NATURE REVIEWS GENETICS, 2012, 13 (01) :7-13
[7]   Activation-induced cytidine deaminase deaminates deoxycytidine on single-stranded DNA but requires the action of RNase [J].
Bransteitter, R ;
Pham, P ;
Scharff, MD ;
Goodman, MF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (07) :4102-4107
[8]  
BRIGGS ROBERT, 1957, J MORPH, V100, P269, DOI 10.1002/jmor.1051000204
[9]   Sheep cloned by nuclear transfer from a cultured cell line [J].
Campbell, KHS ;
McWhir, J ;
Ritchie, WA ;
Wilmut, I .
NATURE, 1996, 380 (6569) :64-66
[10]   Gene expression - The amazing demethylase [J].
Cedar, H ;
Verdine, GL .
NATURE, 1999, 397 (6720) :568-569