Differential effects of AdOx on gene expression in P19 embryonal carcinoma cells.
BACKGROUND
Pluripotent cells maintain a unique gene expression pattern and specific chromatin signature. In this study, we explored the effect of the methyltransferase inhibitor adenosine dialdehyde (AdOx) on pluripotency maintenance and gene expression in P19 embryonal carcinoma cells.


RESULTS
After AdOx treatment, the pluripotency-related gene network became disordered, and the early developmental genes were released from the repression. Remarkably, AdOx caused contrasting effects on the expression of two key pluripotency genes, nanog and oct3/4, with the reduction of the repressive histone marks H3K27me3, H3K9me3 and H3K9me2 only in the nanog gene.


CONCLUSIONS
Key pluripotency genes were controlled by different mechanisms, including the differential enrichment of repressive histone methylation marks. These data provided novel clues regarding the critical role of histone methylation in the maintenance of pluripotency and the determination of cell fate in P19 pluripotent cells.
National Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College, 5 Dongdan Santiao, Beijing 100005, China.
Li
L
Yan
Hai-Yong
HY
Zhao
Ye
Y
Zhang
Yu-Fei
YF
Shen
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism*; D013997:Time Factors; D014212:Tretinoin / Q000494:pharmacology
D000241:Adenosine; D051792:Basic Helix-Loop-Helix Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D018398:Homeodomain Proteins; D000071317:Nanog Homeobox Protein; D009419:Nerve Tissue Proteins; D050814:Octamer Transcription Factor-3; D014212:Tretinoin; C499317:Ascl1 protein, mouse; C475540:Nanog protein, mouse; C494174:Pou5f1 protein, mouse; C093564:Neurogenic differentiation factor 1; C027579:periodate-oxidized adenosine