Details

Autor(en) / Beteiligte

• Shapira, Suzanne N
• Lim, Hee-Woong
• Rajakumari, Sona
• Sakers, Alexander P
• Ishibashi, Jeff
• Harms, Matthew J
• Won, Kyoung-Jae
• Seale, Patrick

Titel

EBF2 transcriptionally regulates brown adipogenesis via the histone reader DPF3 and the BAF chromatin remodeling complex

Ist Teil von

• Genes & development, 2017-04, Vol.31 (7), p.660-673

Ort / Verlag

United States: Cold Spring Harbor Laboratory Press

Erscheinungsjahr

2017

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• The transcription factor early B-cell factor 2 (EBF2) is an essential mediator of brown adipocyte commitment and terminal differentiation. However, the mechanisms by which EBF2 regulates chromatin to activate brown fat-specific genes in adipocytes were unknown. ChIP-seq (chromatin immunoprecipitation [ChIP] followed by deep sequencing) analyses in brown adipose tissue showed that EBF2 binds and regulates the activity of lineage-specific enhancers. Mechanistically, EBF2 physically interacts with the chromatin remodeler BRG1 and the BAF chromatin remodeling complex in brown adipocytes. We identified the histone reader protein DPF3 as a brown fat-selective component of the BAF complex that was required for brown fat gene programming and mitochondrial function. Loss of DPF3 in brown adipocytes reduced chromatin accessibility at EBF2-bound enhancers and led to a decrease in basal and catecholamine-stimulated expression of brown fat-selective genes. Notably, is a direct transcriptional target of EBF2 in brown adipocytes, thereby establishing a regulatory module through which EBF2 activates and also recruits DPF3-anchored BAF complexes to chromatin. Together, these results reveal a novel mechanism by which EBF2 cooperates with a tissue-specific chromatin remodeling complex to activate brown fat identity genes.