Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways

Urs Graf; Elisa A. Casanova; Sarah Wyck; Damian Dalcher; Marco Gatti; Eva Vollenweider; Michal J. Okoniewski; Fabienne A. Weber; Sameera S. Patel; Marc W. Schmid; Jiwen Li; Jafar Sharif; Guido A. Wanner; Haruhiko Koseki; Jiemin Wong; Pawel Pelczar; Lorenza Penengo; Raffaella Santoro; Paolo Cinelli

doi:10.1038/ncb3554

Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways

Urs Graf
, Elisa A. Casanova
, Sarah Wyck
, Damian Dalcher
, Marco Gatti
, Eva Vollenweider
, Michal J. Okoniewski
, Fabienne A. Weber
, Sameera S. Patel
, Marc W. Schmid
, Jiwen Li
, Jafar Sharif
, Guido A. Wanner
, Haruhiko Koseki
, Jiemin Wong
, Pawel Pelczar
, Lorenza Penengo
, Raffaella Santoro^*
, Paolo Cinelli

^*Corresponding author for this work

School of Life Sciences

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

Abstract

Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance. Increasing Pramel7 expression in serum-cultured ESCs promotes a preimplantation epiblast-like gene signature, reduces UHRF1 levels and causes global DNA hypomethylation. Pramel7 is required for blastocyst formation and its forced expression locks ESCs in pluripotency. Pramel7/UHRF1 expression is mutually exclusive in ICMs whereas Pramel7-knockout embryos express high levels of UHRF1. Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency.

Original language	English
Pages (from-to)	763-773
Number of pages	11
Journal	Nature Cell Biology
Volume	19
Issue number	7
DOIs	https://doi.org/10.1038/ncb3554
State	Published - 1 Jul 2017

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Graf, U., Casanova, E. A., Wyck, S., Dalcher, D., Gatti, M., Vollenweider, E., Okoniewski, M. J., Weber, F. A., Patel, S. S., Schmid, M. W., Li, J., Sharif, J., Wanner, G. A., Koseki, H., Wong, J., Pelczar, P., Penengo, L., Santoro, R., & Cinelli, P. (2017). Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways. Nature Cell Biology, 19(7), 763-773. https://doi.org/10.1038/ncb3554

@article{b8bddc9d1d1748f79769fc173e1aeda2,

title = "Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways",

abstract = "Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance. Increasing Pramel7 expression in serum-cultured ESCs promotes a preimplantation epiblast-like gene signature, reduces UHRF1 levels and causes global DNA hypomethylation. Pramel7 is required for blastocyst formation and its forced expression locks ESCs in pluripotency. Pramel7/UHRF1 expression is mutually exclusive in ICMs whereas Pramel7-knockout embryos express high levels of UHRF1. Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency.",

author = "Urs Graf and Casanova, \{Elisa A.\} and Sarah Wyck and Damian Dalcher and Marco Gatti and Eva Vollenweider and Okoniewski, \{Michal J.\} and Weber, \{Fabienne A.\} and Patel, \{Sameera S.\} and Schmid, \{Marc W.\} and Jiwen Li and Jafar Sharif and Wanner, \{Guido A.\} and Haruhiko Koseki and Jiemin Wong and Pawel Pelczar and Lorenza Penengo and Raffaella Santoro and Paolo Cinelli",

year = "2017",

month = jul,

day = "1",

doi = "10.1038/ncb3554",

language = "英语",

volume = "19",

pages = "763--773",

journal = "Nature Cell Biology",

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Graf, U, Casanova, EA, Wyck, S, Dalcher, D, Gatti, M, Vollenweider, E, Okoniewski, MJ, Weber, FA, Patel, SS, Schmid, MW, Li, J, Sharif, J, Wanner, GA, Koseki, H, Wong, J, Pelczar, P, Penengo, L, Santoro, R & Cinelli, P 2017, 'Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways', Nature Cell Biology, vol. 19, no. 7, pp. 763-773. https://doi.org/10.1038/ncb3554

TY - JOUR

T1 - Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways

AU - Graf, Urs

AU - Casanova, Elisa A.

AU - Wyck, Sarah

AU - Dalcher, Damian

AU - Gatti, Marco

AU - Vollenweider, Eva

AU - Okoniewski, Michal J.

AU - Weber, Fabienne A.

AU - Patel, Sameera S.

AU - Schmid, Marc W.

AU - Li, Jiwen

AU - Sharif, Jafar

AU - Wanner, Guido A.

AU - Koseki, Haruhiko

AU - Wong, Jiemin

AU - Pelczar, Pawel

AU - Penengo, Lorenza

AU - Santoro, Raffaella

AU - Cinelli, Paolo

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance. Increasing Pramel7 expression in serum-cultured ESCs promotes a preimplantation epiblast-like gene signature, reduces UHRF1 levels and causes global DNA hypomethylation. Pramel7 is required for blastocyst formation and its forced expression locks ESCs in pluripotency. Pramel7/UHRF1 expression is mutually exclusive in ICMs whereas Pramel7-knockout embryos express high levels of UHRF1. Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency.

AB - Naive pluripotency is established in preimplantation epiblast. Embryonic stem cells (ESCs) represent the immortalization of naive pluripotency. 2i culture has optimized this state, leading to a gene signature and DNA hypomethylation closely comparable to preimplantation epiblast, the developmental ground state. Here we show that Pramel7 (PRAME-like 7), a protein highly expressed in the inner cell mass (ICM) but expressed at low levels in ESCs, targets for proteasomal degradation UHRF1, a key factor for DNA methylation maintenance. Increasing Pramel7 expression in serum-cultured ESCs promotes a preimplantation epiblast-like gene signature, reduces UHRF1 levels and causes global DNA hypomethylation. Pramel7 is required for blastocyst formation and its forced expression locks ESCs in pluripotency. Pramel7/UHRF1 expression is mutually exclusive in ICMs whereas Pramel7-knockout embryos express high levels of UHRF1. Our data reveal an as-yet-unappreciated dynamic nature of DNA methylation through proteasome pathways and offer insights that might help to improve ESC culture to reproduce in vitro the in vivo ground-state pluripotency.

UR - https://www.scopus.com/pages/publications/85021700081

U2 - 10.1038/ncb3554

DO - 10.1038/ncb3554

M3 - 文章

C2 - 28604677

AN - SCOPUS:85021700081

SN - 1465-7392

VL - 19

SP - 763

EP - 773

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 7

ER -

Pramel7 mediates ground-state pluripotency through proteasomal-epigenetic combined pathways

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