Aberrant epigenetic changes and gene expression in cloned cattle dying around birth.
BACKGROUND
Aberrant reprogramming of donor somatic cell nuclei may result in many severe problems in animal cloning. To assess the extent of abnormal epigenetic modifications and gene expression in clones, we simultaneously examined DNA methylation, histone H4 acetylation and expression of six genes (beta-actin, VEGF, oct4, TERT, H19 and Igf2) and a repetitive sequence (art2) in five organs (heart, liver, spleen, lung and kidney) from two cloned cattle groups that had died at different stages. In the ED group (early death, n = 3), the cloned cattle died in the perinatal period. The cattle in the LD group (late death, n = 3) died after the perinatal period. Normally reproduced cattle served as a control group (n = 3).


RESULTS
Aberrant DNA methylation, histone H4 acetylation and gene expression were observed in both cloned groups. The ED group showed relatively fewer severe DNA methylation abnormalities (p < 0.05) but more abnormal histone H4 acetylations (p < 0.05) and more abnormal expression (p < 0.05) of the selected genes compared to the LD group. However, our data also suggest no widespread gene expression abnormalities in the organs of the dead clones.


CONCLUSIONS
Deaths of clones may be ascribed to abnormal expression of a very limited number of genes.
Lin
Li
L
State Key Laboratory for Agrobiotechnology, China Agricultural University, Yuanmingyuan West Road 2, Beijing 100094, PR China. linlicau@yahoo.com.cn
Li
Qiang
Q
Zhang
Lei
L
Zhao
Dingsheng
D
Dai
Yunping
Y
Li
Ning
N
D000107:Acetylation; D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002417:Cattle / Q000235:genetics*; D019976:Cloning, Organism; D019175:DNA Methylation; D044127:Epigenesis, Genetic / Q000235:genetics*; D005313:Fetal Death / Q000235:genetics*; D018507:Gene Expression Regulation, Developmental; D006657:Histones; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism; D009928:Organ Specificity; D036801:Parturition; D012091:Repetitive Sequences, Nucleic Acid; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
D000199:Actins; D006657:Histones; D042461:Vascular Endothelial Growth Factor A; D007335:Insulin-Like Growth Factor II