Krox20 Hindbrain Regulation Incorporates Multiple Modes of Cooperation Between Cis-acting Elements

Overview

Journal PLoS Genet

Specialty Genetics

Date 2017 Jul 28

PMID 28749941

Citations 12

Authors

Elodie Thierion

Johan Le Men

Samuel Collombet

Celine Hernandez

Fanny Coulpier

Patrick Torbey

Morgane Thomas-Chollier

Daan Noordermeer

Patrick Charnay

Pascale Gilardi-Hebenstreit

Affiliations

Soon will be listed here.

Abstract

Developmental genes can harbour multiple transcriptional enhancers that act simultaneously or in succession to achieve robust and precise spatiotemporal expression. However, the mechanisms underlying cooperation between cis-acting elements are poorly documented, notably in vertebrates. The mouse gene Krox20 encodes a transcription factor required for the specification of two segments (rhombomeres) of the developing hindbrain. In rhombomere 3, Krox20 is subject to direct positive feedback governed by an autoregulatory enhancer, element A. In contrast, a second enhancer, element C, distant by 70 kb, is active from the initiation of transcription independent of the presence of the KROX20 protein. Here, using both enhancer knock-outs and investigations of chromatin organisation, we show that element C possesses a dual activity: besides its classical enhancer function, it is also permanently required in cis to potentiate the autoregulatory activity of element A, by increasing its chromatin accessibility. This work uncovers a novel, asymmetrical, long-range mode of cooperation between cis-acting elements that might be essential to avoid promiscuous activation of positive autoregulatory elements.

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