Figure 5. BET proteins co-regulate transcriptional networks of transcriptional activation and repression.

Several functional networks are co-regulated by BET protein interactions. Some interactions involve transcriptional co-repression, such as insulin transcription⁶⁵, peroxisome proliferator-activated receptor-γ (PPARγ)-controlled adipogenic differentiation in adipose tissue^65,118 and GATA1-controlled haematopoietic differentiation^143,144. Other interactions involve transcriptional co-activation, such as the activation of genes that promote cell cycle progression controlled by MYC^81,84,92,96 and E2F proteins^{28,29,34,37,38}; nuclear factor-κB (NF-κB)-controlled synthesis of pro-inflammatory cytokines^{65,97,101,102}; and cellular genes regulated by P-TEFb. The transcription and replication of latent viruses seem to exploit BET protein capacity for either co-repression or co-activation, depending on the demands of the virus, through P-TEFb^{40,44,45,47,171}, human papilloma virus (HPV) E2 protein^157–165 or Kaposi’s sarcoma-associated herpesvirus (KSHV) LANA1 protein^61,166–170. Recent data also implicate BRD4 in the maintenance of higher order chromatin structure. EBV, Epstein–Barr virus.