Bicoid-nucleosome Competition Sets a Concentration Threshold for Transcription Constrained by Genome Replication

Overview

Journal bioRxiv

Date 2024 Dec 23

PMID 39713295

Authors

Eleanor A Degen

Corinne Croslyn

Niall M Mangan

Shelby A Blythe

Affiliations

Soon will be listed here.

Abstract

Transcription factors (TFs) regulate gene expression despite constraints from chromatin structure and the cell cycle. Here we examine the concentration-dependent regulation of by the Bicoid morphogen through a combination of quantitative imaging, mathematical modeling and epigenomics in embryos. By live imaging of MS2 reporters, we find that, following mitosis, the timing of transcriptional activation driven by the P2 ( P2) enhancer directly reflects Bicoid concentration. We build a stochastic model that can explain onset time distributions by accounting for both the competition between Bicoid and nucleosomes at P2 and a negative influence of DNA replication on transcriptional elongation. Experimental modulation of nucleosome stability alters onset time distributions and the posterior boundary of expression. We conclude that TF-nucleosome competition is the molecular mechanism whereby the Bicoid morphogen gradient specifies the posterior boundary of expression.

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