The FBXL10/KDM2B Scaffolding Protein Associates with Novel Polycomb Repressive Complex-1 to Regulate Adipogenesis

Overview

Journal J Biol Chem

Specialty Biochemistry

Date 2014 Dec 24

PMID 25533466

Citations 20

Authors

Takeshi Inagaki

Satoshi Iwasaki

Yoshihiro Matsumura

Takeshi Kawamura

Toshiya Tanaka

Yohei Abe

Ayumu Yamasaki

Yuya Tsurutani

Ayano Yoshida

Yoko Chikaoka

Kanako Nakamura

Kenta Magoori

Ryo Nakaki

Timothy F Osborne

Kiyoko Fukami

Hiroyuki Aburatani

Tatsuhiko Kodama

Juro Sakai

Affiliations

Soon will be listed here.

Abstract

Polycomb repressive complex 1 (PRC1) plays an essential role in the epigenetic repression of gene expression during development and cellular differentiation via multiple effector mechanisms, including ubiquitination of H2A and chromatin compaction. However, whether it regulates the stepwise progression of adipogenesis is unknown. Here, we show that FBXL10/KDM2B is an anti-adipogenic factor that is up-regulated during the early phase of 3T3-L1 preadipocyte differentiation and in adipose tissue in a diet-induced model of obesity. Interestingly, inhibition of adipogenesis does not require the JmjC demethylase domain of FBXL10, but it does require the F-box and leucine-rich repeat domains, which we show recruit a noncanonical polycomb repressive complex 1 (PRC1) containing RING1B, SKP1, PCGF1, and BCOR. Knockdown of either RING1B or SKP1 prevented FBXL10-mediated repression of 3T3-L1 preadipocyte differentiation indicating that PRC1 formation mediates the inhibitory effect of FBXL10 on adipogenesis. Using ChIP-seq, we show that FBXL10 recruits RING1B to key specific genomic loci surrounding the key cell cycle and the adipogenic genes Cdk1, Uhrf1, Pparg1, and Pparg2 to repress adipogenesis. These results suggest that FBXL10 represses adipogenesis by targeting a noncanonical PRC1 complex to repress key genes (e.g. Pparg) that control conversion of pluripotent cells into the adipogenic lineage.

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