A transcriptional cyclin, Cyclin G,
participates in growth homeostasis1. Indeed, the over-expression of
this cyclin in a population of isogenic flies grown in a standardized
environment increase organ fluctuating asymmetry, a stochastic asymmetry resulting
from disruption of growth homeostasis1. We have used Cyclin G
mis-expression as a sensitized system to identify the genetic and epigenetic
bases of growth homeostasis (large scale screen and candidate gene approach).
Cyclin G interacts with several factors known to model the epigenome. Indeed,
it interacts genetically with the chromatin complexes Polycomb and Trithorax
and physically with two of their cofactors, Corto and ASX2. We have
shown recently that Cyclin G interacts with particular Polycomb complexes in
the control of growth homeostasis. Another original result obtained in our team
is the role of a ribosomal protein, RPL12, in the control of gene transcription3.
This function is linked to the direct interaction between the chromodomain of
Corto and a methylated form of RPL12 (RPL12K3me3). Through RNA-seq experiments,
we have shown that Corto, RPL12 and Cyclin G regulate the expression of genes
involved in ribosome biogenesis. Thus, a network centered on these three nodes
might maintain growth homeostasis through an epigenetic control of ribosome
biogenesis. Currently, we are identifying the genetic and physical interactors
of these nodes to extend the network.
We have identified a few members of a gene
regulatory network that controls pigmentation and is sensitive to temperature4.
To complete this network, we have first analysed the transcriptome of the
posterior abdomen epithelium from females grown at different temperatures
(pupae and young adults). These experiments have revealed that tan, that encodes an enzyme involved in
melanin production, is a major effector of this network5. yellow, that encodes another
pigmentation enzyme, is also involved but to a lesser extent6. We
have shown that the activity of a tan
enhancer, t-MSE, is modulated by
temperature5. The thermal plasticity of tan expression is correlated with the level of the active
epigenetic mark H3K4me3 on its promoter. This mark is apposed by Trithorax.
H3K4me3 might represent a universal plasticity mark as similar results were
obtained in other organisms. Through complementary experiments (yeast simple
hybrid, genetic screen targeting transcription factors and chromatin
regulators, reaction norms), we have identified several regulators of tan that are sensitive to temperature.
We are currently performing epistasis experiments with these genes to build the
regulatory gene network of pigmentation plasticity. Our final goal is to model
this network. In addition, we have analysed the effect of natural genetic
variation in tan enhancer using
transgenic lines7. The fact that the same regulatory sequence
mediates the effect of the environment and is involved in evolution lead us to think
about the link between phenotypic plasticity and evolution8.
- 1Debat et al. (2011)
PLoS Genet 7, e1002314
- 2Dupont et al. (2015)
Epigenetics & Chromatin 8, 18
- 3Coléno-Costes et al.
(2012) PLoS Genet 8, e1003006
- 4Gibert et al. (2007) PLoS Genet 3, e30
- 5Gibert et al.
(2016) PLoS Genet 12, e1006218
- 6Gibert et al.,
(2017) Sci Rep 7 :43370
- 7Gibert et al.
(2017) Genome Biol 18(1)
- 8Gibert (2017) Dev Genes Evol : Aug 6