TY - JOUR
T1 - Tsix RNA and the germline factor, PRDM14, link X reactivation and stem cell reprogramming
AU - Payer, Bernhard
AU - Rosenberg, Michael
AU - Yamaji, Masashi
AU - Yabuta, Yukihiro
AU - Koyanagi-Aoi, Michiyo
AU - Hayashi, Katsuhiko
AU - Yamanaka, Shinya
AU - Saitou, Mitinori
AU - Lee, Jeannie T.
N1 - Funding Information:
We are grateful to all members of the Lee Lab for valuable discussions and suggestions. We would like to thank M. Stadtfeld, J. Polo, N. Maherali, E. Apostolou, M. Anguera, and K. Hochedlinger for critical advice on iPSC reprogramming; L. Prickett-Rice, S. Lahiri, M. Weglarz, and K. Folz-Donahue for cell sorting; H. Sunwoo for Xist-LNA probe; and Y. Ogawa for Xist-DNA probe. B.P. was funded by postdoctoral awards from the Human Frontier Science Program and the Charles A. King Trust, Bank of America, Co-Trustee. J.T.L. is supported by the NIH (R37-GM58839). J.T.L. is an Investigator of the Howard Hughes Medical Institute. S.Y. is a member without salary of the scientific advisory boards of iPierian, iPS Academia Japan, Megakaryon Corporation, and HEALIOS K. K. Japan.
PY - 2013/12/26
Y1 - 2013/12/26
N2 - Transitions between pluripotent and differentiated states are marked by dramatic epigenetic changes. Cellular differentiation is tightly linked to X chromosome inactivation (XCI), whereas reprogramming to induced pluripotent stem cells (iPSCs) is associated with X chromosome reactivation (XCR). XCR reverses the silent state of the inactive X, occurring in mouse blastocysts and germ cells. In spite of its importance, little is known about underlying mechanisms. Here, we examine the role of the long noncoding Tsix RNA and the germline factor, PRDM14. In blastocysts, XCR is perturbed by mutation of either Tsix or Prdm14. In iPSCs, XCR is disrupted only by PRDM14 deficiency, which also affects iPSC derivation and maintenance. We show that Tsix and PRDM14 directly link XCR to pluripotency: first, PRDM14 represses Rnf12 by recruiting polycomb repressive complex 2; second, Tsix enables PRDM14 to bind Xist. Thus, our study provides functional and mechanistic links between cellular and X chromosome reprogramming.
AB - Transitions between pluripotent and differentiated states are marked by dramatic epigenetic changes. Cellular differentiation is tightly linked to X chromosome inactivation (XCI), whereas reprogramming to induced pluripotent stem cells (iPSCs) is associated with X chromosome reactivation (XCR). XCR reverses the silent state of the inactive X, occurring in mouse blastocysts and germ cells. In spite of its importance, little is known about underlying mechanisms. Here, we examine the role of the long noncoding Tsix RNA and the germline factor, PRDM14. In blastocysts, XCR is perturbed by mutation of either Tsix or Prdm14. In iPSCs, XCR is disrupted only by PRDM14 deficiency, which also affects iPSC derivation and maintenance. We show that Tsix and PRDM14 directly link XCR to pluripotency: first, PRDM14 represses Rnf12 by recruiting polycomb repressive complex 2; second, Tsix enables PRDM14 to bind Xist. Thus, our study provides functional and mechanistic links between cellular and X chromosome reprogramming.
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U2 - 10.1016/j.molcel.2013.10.023
DO - 10.1016/j.molcel.2013.10.023
M3 - Article
AN - SCOPUS:84891097289
SN - 1097-2765
VL - 52
SP - 805
EP - 818
JO - Molecular Cell
JF - Molecular Cell
IS - 6
ER -