PRDM14 maintains pluripotency of embryonic stem cells through TET-mediated active DNA demethylation.

Biochemical and Biophysical Research Communications
Naoki OkashitaYoshiyuki Seki

Abstract

Pluripotency and self-renewal of mouse embryonic stem cells (ESCs) depend on a network of transcription factors maintained by exogenous leukaemia inhibitory factor (LIF). PR-domain containing transcriptional regulator 14 (PRDM14), is essential for maintenance of ESC self-renewal when the cells are cultured in serum plus LIF, but not in 2i medium plus LIF. Here, we show that pluripotency of ESCs is maintained by enforced expression of PRDM14 at a high level, as observed in ESCs in 2i plus LIF and developing primordial germ cells in the absence of LIF. Constitutive expression of PRDM14 represses de novo DNA methylation in pluripotency-associated genes, resulting in the maintenance of gene expression after withdrawal of LIF, while also repressing the upregulation of differentiation markers. Further, knockdown of Tet1/Tet2 and administration of base excision repair (BER) pathway inhibitors impairs the PRDM14-induced resistance of ESCs to differentiation. We conclude that, in the absence of LIF, PRDM14 governs the retention of pluripotency-associated genes through the regulation of TET functions in the BER-mediated active demethylation pathway, while acting to exert TET-independent transcriptional repressive activity of several diff...Continue Reading

References

Jul 16, 2008·Nature Genetics·Masashi YamajiMitinori Saitou
Mar 18, 2009·Bioinformatics·Cole TrapnellSteven L Salzberg
May 26, 2011·The Journal of Biological Chemistry·Shannon Morey KinneySriharsa Pradhan

❮ Previous
Next ❯

Citations

Sep 6, 2018·The Journal of Biological Chemistry·Khoa A TranRupa Sridharan
Nov 14, 2018·Cellular and Molecular Life Sciences : CMLS·Seyedeh-Nafiseh HassaniHossein Baharvand
Mar 1, 2018·Frontiers in Cell and Developmental Biology·Yoshiyuki Seki
Dec 17, 2020·Cell Biology International·Narges DastmalchiReza Safaralizadeh
Aug 2, 2020·Seminars in Cancer Biology·Ammad Ahmad FarooqiMassimo Mallardo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiovascular Disease & TET2

Cardiovascular diseases are the number one cause of deaths globally. Tet methylcytosine dioxygenase 2 (TET2)-mediated hematopoiesis has been implicated in accelerating heart failure. Here is the latest research on cardiovascular diseases and TET2.