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HIF-2? regulates NANOG expression in human embryonic stem cells following hypoxia and reoxygenation through the interaction with an Oct-Sox Cis regulatory element

HIF-2? regulates NANOG expression in human embryonic stem cells following hypoxia and reoxygenation through the interaction with an Oct-Sox Cis regulatory element
HIF-2? regulates NANOG expression in human embryonic stem cells following hypoxia and reoxygenation through the interaction with an Oct-Sox Cis regulatory element
Low O2 tension is beneficial for human embryonic stem cell (hESC) maintenance but the mechanism of regulation is unknown. HIF-2? was found to bind directly to predicted hypoxic response elements (HREs) in the proximal promoter of OCT4, NANOG and SOX2 only in hESCs cultured under hypoxia (5% O2). This binding induced an array of histone modifications associated with gene transcription while a heterochromatic state existed at atmospheric O2. Interestingly, an enhanced euchromatic state was found when hESCs were exposed to hypoxia followed by 72 hours reoxygenation. This was sustained by HIF-2? which enhanced stemness by binding to an oct-sox cis-regulatory element in the NANOG promoter. Thus, these data have uncovered a novel role of HIF-2? as a direct regulator of key transcription factors controlling self-renewal in hESCs but also in the induction of epigenetic modifications ensuring a euchromatic conformation which enhances the regenerative potential of these cells.
1932-6203
e108309
Petruzzelli, Raffaella
4173c3a0-43ba-4fef-8eb9-ee055a94bd62
Christensen, David R.
f8d74902-963b-433c-98ba-11e13700f2df
Parry, Kate L.
7180a304-dd45-4d0f-aed3-75b52d62a786
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Houghton, Franchesca D.
53946041-127e-45a8-9edb-bf4b3c23005f
Petruzzelli, Raffaella
4173c3a0-43ba-4fef-8eb9-ee055a94bd62
Christensen, David R.
f8d74902-963b-433c-98ba-11e13700f2df
Parry, Kate L.
7180a304-dd45-4d0f-aed3-75b52d62a786
Sanchez-Elsner, Tilman
b8799f8d-e2b4-4b37-b77c-f2f0e8e2070d
Houghton, Franchesca D.
53946041-127e-45a8-9edb-bf4b3c23005f

Petruzzelli, Raffaella, Christensen, David R., Parry, Kate L., Sanchez-Elsner, Tilman and Houghton, Franchesca D. (2014) HIF-2? regulates NANOG expression in human embryonic stem cells following hypoxia and reoxygenation through the interaction with an Oct-Sox Cis regulatory element. PLoS ONE, 9 (10), e108309. (doi:10.1371/journal.pone.0108309). (PMID:25271810)

Record type: Article

Abstract

Low O2 tension is beneficial for human embryonic stem cell (hESC) maintenance but the mechanism of regulation is unknown. HIF-2? was found to bind directly to predicted hypoxic response elements (HREs) in the proximal promoter of OCT4, NANOG and SOX2 only in hESCs cultured under hypoxia (5% O2). This binding induced an array of histone modifications associated with gene transcription while a heterochromatic state existed at atmospheric O2. Interestingly, an enhanced euchromatic state was found when hESCs were exposed to hypoxia followed by 72 hours reoxygenation. This was sustained by HIF-2? which enhanced stemness by binding to an oct-sox cis-regulatory element in the NANOG promoter. Thus, these data have uncovered a novel role of HIF-2? as a direct regulator of key transcription factors controlling self-renewal in hESCs but also in the induction of epigenetic modifications ensuring a euchromatic conformation which enhances the regenerative potential of these cells.

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e-pub ahead of print date: 1 October 2014
Published date: 1 October 2014
Organisations: Human Development & Health, Clinical & Experimental Sciences

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Local EPrints ID: 369625
URI: https://eprints.soton.ac.uk/id/eprint/369625
ISSN: 1932-6203
PURE UUID: d8bbf75a-a03e-44ad-b402-1e7e97626c8d

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Date deposited: 08 Oct 2014 11:58
Last modified: 04 Nov 2019 20:23

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