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Context-Dependent Functions of NANOG Phosphorylation in Pluripotency and Reprogramming.

Abstract：

:The core pluripotency transcription factor NANOG is critical for embryonic stem cell (ESC) self-renewal and somatic cell reprogramming. Although NANOG is phosphorylated at multiple residues, the role of NANOG phosphorylation in ESC self-renewal is incompletely understood, and no information exists regarding its functions during reprogramming. Here we report our findings that NANOG phosphorylation is beneficial, although nonessential, for ESC self-renewal, and that loss of phosphorylation enhances NANOG activity in reprogramming. Mutation of serine 65 in NANOG to alanine (S65A) alone has the most significant impact on increasing NANOG reprogramming capacity. Mechanistically, we find that pluripotency regulators (ESRRB, OCT4, SALL4, DAX1, and TET1) are transcriptionally primed and preferentially associated with NANOG S65A at the protein level due to presumed structural alterations in the N-terminal domain of NANOG. These results demonstrate that a single phosphorylation site serves as a critical interface for controlling context-dependent NANOG functions in pluripotency and reprogramming.

journal_name

Stem Cell Reports

journal_title

Stem cell reports

authors

Saunders A,Li D,Faiola F,Huang X,Fidalgo M,Guallar D,Ding J,Yang F,Xu Y,Zhou H,Wang J

doi

10.1016/j.stemcr.2017.03.023

subject

Has Abstract

pub_date

2017-05-09 00:00:00

pages

1115-1123

issue

5

issn

2213-6711

pii

S2213-6711(17)30129-7

journal_volume

8

pub_type

杂志文章

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