The proinflammatory cytokine tumor necrosis factor (TNF) plays a central role in 
low-grade adipose tissue inflammation and development of insulin resistance 
during obesity. In this context, nuclear factor κ-light-chain-enhancer of 
activated B cells (NFκB) is directly involved and required for the acute 
activation of the inflammatory gene program. Here, we show that the major 
transactivating subunit of NFκB, v-rel avian reticuloendotheliosis viral 
oncogene homolog A (RELA), is also required for acute TNF-induced suppression of 
adipocyte genes. Notably, this repression does not involve RELA binding to the 
associated enhancers but rather loss of cofactors and enhancer RNA (eRNA) 
selectively from high-occupancy sites within super-enhancers. Based on these 
data, we have developed models that, with high accuracy, predict which enhancers 
and genes are repressed by TNF in adipocytes. We show that these models are 
applicable to other cell types where TNF represses genes associated with 
super-enhancers in a highly cell-type-specific manner. Our results propose a 
novel paradigm for NFκB-mediated repression, whereby NFκB selectively 
redistributes cofactors from high-occupancy enhancers, thereby specifically 
repressing super-enhancer-associated cell identity genes.