On the role of transcription in positioning nucleosomes

Abstract

Nucleosome positioning is crucial for the genome’s function. Though the role of DNA sequence in positioning nucleosomes is well understood, a detailed mechanistic understanding on the impact of transcription remains lacking. Using numerical simulations, we investigated the dependence of nucleosome density profiles on transcription level across multiple species. We found that the low nucleosome affinity of yeast, but not mouse, promoters contributes to the formation of phased nucleosomes arrays for inactive genes. For the active genes, a heterogeneous distribution of +1 nucleosomes, caused by a tug-of-war between two types of remodeling enzymes, is essential for reproducing their density profiles. In particular, while positioning enzymes are known to remodel the +1 nucleosome and align it toward the transcription start site (TSS), spacer enzymes that use a pair of nucleosomes as their substrate can shift the nucleosome array away from the TSS. Competition between these enzymes results in two types of nucleosome density profiles with well- and ill-positioned +1 nucleosome. Finally, we showed that Pol II assisted histone exchange, if occurring at a fast speed, can abolish the impact of remodeling enzymes. By elucidating the role of individual factors, our study reconciles the seemingly conflicting results on the overall impact of transcription in positioning nucleosomes across species.

Phase Separation and Correlated Motions in Motorized Genome

“…The cell nucleus is an active system enriched with ATP-driven processes. The ideal potential was specifically designed to account for the role of molecular motors like cohesin that can compact individual chromosomes. , Other active processes, including transcription and nucleosome remodeling, ,,− can also lead to nonconservative forces to perturb chromosome structures. The effect of these processes, together with passive interactions arising from epigenetic modifications and chromatin regulators, may produce the effective compartment specific potential inferred from Hi-C data.…”

Viral reprogramming of host transcription initiation

“…To further assess proximity to active TSSs, we determined the relationship between de novo promoter TSSs and positioned nucleosomes since positioned nucleosomes are typically present within the first 150 bp downstream from TSSs ( 42 ). Information on positioned nucleosomes across a genome can be derived from ATAC-seq data based on nucleosome length fragment size enrichment.…”

Transcriptional repression across mitosis: mechanisms and functions

“…A large transcriptional inhibition might favor the complete resetting on the chromatin–chromatin contact network as cells transit through mitosis by fully dismantling fine-scale transcription-dependent interactions. Finally, it is important to note that transcription highly influences nucleosome positioning [ 42 , 43 ], which has been recently shown to play a role on 3D genome organization [ 44 ]. Repressing most transcription early in mitosis would potentially influence nucleosome rearrangement and genome organization during the transit of cells through mitosis.…”