MicroRNA-29b/Tet1 regulatory axis epigenetically modulates mesendoderm differentiation in mouse embryonic stem cells
Publication in refereed journal


摘要Ten eleven translocation ( Tet) family- mediated DNA oxidation on 5- methylcytosine ( 5mC) to 5hydroxymethylcytosine ( 5hmC) represents a novel epigenetic modification that regulates dynamic gene expression during embryonic stem cells ( ESCs) differentiation. Through the role of Tet on 5hmC regulation in stem cell development is relatively defined, how the Tet family is regulated and impacts on ESCs lineage development remains elusive. In this study, we show non- coding RNA regulation on Tet family may contribute to epigenetic regulation during ESCs differentiation, which is suggested by microRNA- 29b ( miR- 29b) binding sites on the Tet1 3 ' untranslated region ( 3' UTR). We demonstrate miR- 29b increases sharply after embyoid body ( EB) formation, which causes Tet1 repression and reduction of cellular 5hmC level during ESCs differentiation. Importantly, we show this miR- 29b/ Tet1 regulatory axis promotes themesendoderm lineage formation both in vitro and in vivo by inducing the Nodal signaling pathway and repressing the key target of the active demethylation pathway, Tdg. Taken together, our findings underscore the contribution of small non- coding RNA mediated regulation on DNA demethylation dynamics and the differential expressions of key mesendoderm regulators during ESCs lineage specification. MiR- 29b could potentially be applied to enrich production of mesoderm and endoderm derivatives and be further differentiated into desired organ- specific cells.
著者Tu JJ, Ng SH, Luk ACS, Liao JY, Jiang XH, Feng B, Mak KKL, Rennert OM, Chan WY, Lee TL
期刊名稱Nucleic Acids Research
詳細描述doi: 10.1093/nar/gkv653.
出版社Oxford University Press (OUP): Policy C - Option B / Oxford University Press
頁次7805 - 7822
Web of Science 學科類別Biochemistry & Molecular Biology

上次更新時間 2021-02-03 於 00:41