RNA-Independent Cis-Autoregulatory Circuits within Bidirectional Gene Pairs Control Metabolism

During metabolic transitions, most pairs are coordinately regulated in liver, in part through chromatin topology. In pairs composed of a long non-coding RNA (lncRNA) and a protein-coding gene (PCG), lncRNA transcription cis-activates PCG transcription by establishing an active chromatin environment at the promoter-proximal enhancer of PCG.

Reciprocally, PCG transcription cis-inhibits lncRNA transcription, forming internal cis-autoregulatory circuits. Interestingly, both directions of regulation are independent of the RNA products, but dependent on the transcription process itself. Similar promoter-proximal enhancer signatures and cis-autoregulatory circuits are present in many lncRNA/PCG and PCG/PCG pairs, underscoring the generalizability of these circuits.