S6K1 Phosphorylation of H2B Mediates EZH2 Trimethylation of H3: A Determinant of Early Adipogenesis

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2016 May 7

PMID 27151441

Citations 53

Authors

Sang Ah Yi

Sung Hee Um

Jaecheol Lee

Ji Hee Yoo

So Young Bang

Eun Kyung Park

Min Gyu Lee

Ki Hong Nam

Ye Ji Jeon

Jong Woo Park

Jueng Soo You

Sang-Jin Lee

Gyu-Un Bae

Jong Won Rhie

Sara C Kozma

George Thomas

Jeung-Whan Han

Affiliations

Soon will be listed here.

Abstract

S6K1 has been implicated in a number of key metabolic responses, which contribute to obesity. Critical among these is the control of a transcriptional program required for the commitment of mesenchymal stem cells to the adipocytic lineage. However, in contrast to its role in the cytosol, the functions and targets of nuclear S6K1 are unknown. Here, we show that adipogenic stimuli trigger nuclear translocation of S6K1, leading to H2BS36 phosphorylation and recruitment of EZH2 to H3, which mediates H3K27 trimethylation. This blocks Wnt gene expression, inducing the upregulation of PPARγ and Cebpa and driving increased adipogenesis. Consistent with this finding, white adipose tissue from S6K1-deficient mice exhibits no detectable H2BS36 phosphorylation or H3K27 trimethylation, whereas both responses are highly elevated in obese humans or in mice fed a high-fat diet. These findings define an S6K1-dependent mechanism in early adipogenesis, contributing to the promotion of obesity.

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