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Phenotypic instability of patchwork mutation: an epigenetic effect?

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HAL Id: hal-02815433

https://hal.inrae.fr/hal-02815433

Submitted on 6 Jun 2020

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Phenotypic instability of patchwork mutation: an epigenetic effect?

Geneviève Aubin Houzelstein, Pierrick Salaun, Laurent Guillaud, Jean-Jacques Panthier

To cite this version:

Geneviève Aubin Houzelstein, Pierrick Salaun, Laurent Guillaud, Jean-Jacques Panthier. Phenotypic

instability of patchwork mutation: an epigenetic effect?. 13th meeting of the European Society for

Pigment Cell Research, Sep 2006, Barcelone, Spain. pp.1, 2006. �hal-02815433�

(2)

PHENOTYPIC INSTABILITY OF PATCHWORK MUTATION : AN EPIGENETIC EFFECT ?

Geneviève Aubin-Houzelstein (1), Pierrick Salaün (1), Laurent Guillaud (1), and Jean-Jacques Panthier (1, 2)

1. Cellular and Molecular Genetics UMR 955 INRA-ENVA, Ecole Nationale Vétérinaire d’Alfort, 7 avenue du Général-de-Gaulle, 94704 Maisons-Alfort cedex, France.

2. Mouse functional Genetics Unit, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris cedex 15, France.

PRM/Alf mice are homozygous for patchwork (pwk), a mutation conferring a salt-and-pepper coat color phenotype. In their coat, black hairs are intermingled with white hairs, without any gray hairs

1

. patchwork is also characterized by its phenotypic instability, two thirds of pwk/pwk mice carrying one or more patches of wild-type color on their coat, referred to as reversion patches. No reversion event can be transmitted via the germline.

Microarrays experiments showed a number of genes from the patchwork region that were differentially expressed in the skin of patchwork fetuses compared to controls. Among them, Mbd3, encoding Methyl Binding Protein 3, was found overexpressed in patchwork skin. MBD3 is part of a CpG-methylated DNA binding complex and is involved in chromatin remodeling. Moreover, we performed fluorescent in situ hybridations on PRM/Alf pwk/pwk and C57BL/6N embryonic fibroblasts with three adjacent probes from the patchwork region. We found that chromatin seemed to be more condensed in the patchwork region of PRM/Alf fibroblasts compared to C57BL/6N controls.

We hypothesized that patchwork DNA methylation status may be involved in patchwork coat color phenotype and reversion rate. To test this hypothesis, we use the same protocol as Waterland et al., who reported that a diet supplemented with methyl precursors can enhance the CpG methylation status of the A

vy

locus

2

. We have produced 90 and 107 PRM/Alf mice fed with a methyl precursors supplemented diet and a control diet respectively. We are analyzing the number and size of reversion patches in both populations.

1. Aubin-Houzelstein G, Bernex F, Elbaz C, Panthier JJ (1998). Survival of patchwork melanoblasts is dependent upon their number in the hair follicle at the end of embryogenesis. Dev Biol. 198(2):266- 76.

2. Waterland RA, Jirtle RL (2003). Transposable elements : targets for early nutritional effects on

epigenetic gene regulation.

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