A dimerized HMX1 inhibits EPHA6/epha4b in mouse and zebrafish retinas.

Fabienne Marcelli,Gaëlle Boisset,Daniel F Schorderet

doi:10.1371/journal.pone.0100096

Fabienne Marcelli, Gaëlle Boisset + Show 1 more

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https://doi.org/10.1371/journal.pone.0100096

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Abstract

HMX1 is a homeobox-containing transcription factor implicated in eye development and responsible for the oculo-auricular syndrome of Schorderet-Munier-Franceschetti. HMX1 is composed of two exons with three conserved domains in exon 2, a homeobox and two domains called SD1 and SD2. The function of the latter two domains remains unknown. During retinal development, HMX1 is expressed in a polarized manner and thus seems to play a role in the establishment of retinal polarity although its exact role and mode of action in eye development are unknown. Here, we demonstrated that HMX1 dimerized and that the SD1 and homeodomains are required for this function. In addition, we showed that proper nuclear localization requires the presence of the homeodomain. We also identified that EPHA6, a gene implicated in retinal axon guidance, is one of its targets in eye development and showed that a dimerized HMX1 is needed to inhibit EPHA6 expression.

Highlights

Homeobox-containing transcription factors represent an important class of factors involved in the regulation of embryogenesis and other molecular programs
HMX1 dimerizes through the SD1 and homeobox domains The ability to homo- or heterodimerize has been demonstrated for many transcription factors, including the NKX member NKX2-5, a cardiac homeobox gene that dimerizes through its homeodomain (HD) [15]
The BRET2 technique is based on the energy transfer occurring between the renilla luciferase (RLUC) and the green fluorescent protein (GFP) when they are in close proximity

Summary

Introduction

Homeobox-containing transcription factors represent an important class of factors involved in the regulation of embryogenesis and other molecular programs. HMX1 is a homeobox-containing transcription factor implicated in eye development. In 1992, Stadler et al described a new homeobox gene called GH6. This gene was later renamed HMX1 and was assigned to the NKX5 family, the reason why HMX1 is known as NKX5-3 [1]. The NKX5/HMX family of transcription factors contains a unique homeobox region that is phylogenetically conserved. HMX1, HMX2 and HMX3 contain two other conserved domains called SD1 and SD2, located immediately C-terminally to the homeobox [5]. The function of these domains is still unknown

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