Constraints and limitations on the transcriptional response downstream of the Bicoid morphogen gradient

Tran, Huy; Walczak, Aleksandra M.; Dostatni, Nathalie

doi:10.1101/728840

Cited by 1 publication

(1 citation statement)

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“…We propose that this decay length corresponds to a sub-population of "active" or "effective" Bcd distributed in a much steeper gradient than the Bcd gradient observed using immunofluorescence or GFP tagging which include all Bcd molecules. Bcd molecules have been shown to be heterogenous in intranuclear motility, age and spatial distributions but to date, we do not know which population of Bcd can access the target gene and activate transcription (Tran et al, 2020). The existence of two (or more) Bicoid populations with different mobilities (Abu-Arish et al, 2010;Fradin, 2017;Mir et al, 2018) obviously raises the question of the underlying gradient for each of them.…”

Section: Discussionmentioning

confidence: 99%

Synthetic reconstruction of the hunchback promoter specifies the role of Bicoid, Zelda and Hunchback in the dynamics of its transcription

Fernandes

Tran

Andrieu

et al. 2021

Preprint

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During development, cell identity is established reproducibly among individuals through the expression of specific genes at the correct time and correct location in space. How genes extract and combine both positional and temporal information from different transcription factor (TF) profiles along polarity axes remain largely unexplored. Here, we showcase the classic hunchback gene in fruit fly embryos, with focus on 3 of its main TFs: Bicoid, Zelda and Hunchback proteins. We constructed a series of synthetic MS2 reporters, where the numbers and combination of binding sites for each TF are varied. Using live imaging of transcription dynamics by these synthetic reporters and modeling tools, we show that i) a Bicoid-only synthetic reporter needs 3 more Bicoid binding sites than found in the hunchback promoter to recapitulates almost all spatial features of early hb expression but takes more time to reach steady state; ii) Hunchback and Zelda binding sites combined with Bicoid sites both reduce the time to reach steady state and increase expression at a different step in the activation process: Zld sites lower the Bicoid threshold required for activation while Hb sites increase the polymerase firing rate and reduce bursting; iii) the shift of the Bicoid-only reporter induced by a reduction by half of Bicoid concentrations indicates that the decay length of the Bicoid activity gradient is lower than the decay length of the Bicoid protein gradient. Altogether, this work indicates that Bicoid is the main source of positional information for hunchback expression and places back the Bicoid system within the physical limits of an equilibrium model.

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