The Transcription Factor SUB1 Is a Master Regulator of the Macrophage TLR Response in Atherosclerosis.

ABSTRACT: Toll-like receptor 2 and 4 (TLR2, TLR4) signaling is implicated in atherosclerotic plaque formation. The two-stage master regulator Virtual Inference of Protein-activity by Enriched Regulon (VIPER) analysis of macrophage TLR2 and TLR4 signature genes integrated with coexpression network genes derived from 371 patient-derived carotid specimens identifies activated RNA polymerase II transcriptional coactivator p15 (SUB1/Sub1, PC4) as a master regulon in the atherogenic TLR response. It is found that TLR2 and TLR4 signaling is proinflammatory and proatherosclerotic in chow-fed apolipoprotein E-deficient (ApoE^-/- ) mice. Through transgenic myeloid-specific Sub1 knockout in ApoE^-/- mice, it is discovered that these proatherosclerotic effects of TLR2 and TLR4 signaling are

SUBMITTER: Huang R 

PROVIDER: S-EPMC8498911 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature