Diagenode

A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.


Lacomme M, Medevielle F, Bourbon HM, Thierion E, Kleinjan DJ, Roussat M, Pituello F, Bel-Vialar S

Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.

Tags
Antibody
Microplex Library Preparation kit

Share this article

Published
April, 2018

Source

Products used in this publication

  • ChIP-seq Grade
    C15410037
    H3K4me1 polyclonal antibody
  • ChIP kit icon
    C05010012
    MicroPlex Library Preparation Kit v2 (12 indices)

       Site map   |   Contact us   |   Conditions of sales   |   Conditions of purchase   |   Privacy policy