Crowding-induced transcriptional bursts dictate polymerase and nucleosome density profiles along genes

Crowding-induced transcriptional bursts dictate polymerase and nucleosome density profiles along genes

van den Berg, A.A. (TU Delft BN/Martin Depken Lab)
Depken, S.M. (TU Delft BN/Martin Depken Lab)

2017

During eukaryotic transcription, RNA polymerase (RNAP) translocates along DNA molecules covered with nucleosomes and other DNA binding proteins. Though the interactions between a single nucleosome and RNAP are by now fairly well understood, this understanding has not been synthesized into a description of transcription on crowded genes, where multiple RNAP transcribe through nucleosomes while preserving the nucleosome coverage. We here take a deductive modeling approach to establish the consequences of RNAP–nucleosome interactions for transcription in crowded environments. We show that under physiologically crowded conditions, the interactions of RNAP with nucleosomes induce a strong kinetic attraction between RNAP molecules, causing them to self-organize into stable and moving pelotons. The peloton formation quantitatively explains the observed nucleosome and RNAP depletion close to the initiation site on heavily transcribed genes. Pelotons further translate into short-timescale transcriptional bursts at termination, resulting in burst characteristics consistent with instances of bursty transcription observed in vivo. To facilitate experimental testing of our proposed mechanism, we present several analytic relations that make testable quantitative predictions.

transcription
genetic
crowding
dna
genes
nucleosomes
OA-Fund TU Delft

http://resolver.tudelft.nl/uuid:335e26b3-420e-4cd4-be61-d8dee0f8abb2

https://doi.org/10.1093/nar/gkx513

0305-1048

Nucleic acids research, 45 (13), 7623-7632

Institutional Repository

journal article

© 2017 A.A. van den Berg, S.M. Depken