Our work titled Intragenic enhancers attenuate host gene expression is accepted and is appearing in Molecular cell

Congratulations to all members from Jothi lab whom have worked on this project! It took us a long time but all the hard-work paid off, finally.

Read the paper here.

Abstract

Gene transcription in eukaryotic organisms is regulated at multiple rate-limiting steps, including RNA Polymerase II (RNAPII) recruitment, transcription initiation, promoter-proximal RNAPII pause release, and transcription termination. However, transcriptional regulation during productive elongation remain poorly understood. Enhancers, which activate gene transcription, themselves undergo RNAPII-mediated transcription, but our understanding of enhancer transcription and RNAs (eRNAs) remain incomplete. Here we show that transcription at intragenic enhancers interferes with and attenuates host gene transcription during productive elongation. While the extent of attenuation correlates positively with nascent eRNA expression, the act of transcription at intragenic enhancers, but not the transcript itself, explains the attenuation. Through CRISPR/Cas9-mediated deletions, we demonstrate a physiological role for intragenic enhancer-mediated transcription attenuation in cell-fate determination. Our findings suggest that intragenic enhancers not only enhance transcription of one or more genes from a distance but also fine‐tune transcription of their host gene through attenuation, facilitating differential utilization of the same regulatory element to perform disparate functions.