Long non-coding RNAs and chromatin modifications control long-range regulation of FOXL2, the key gene for ovarian differentiation in goat.
Résumé
PIS (Polled Intersex Syndrome) mutation in goat induces hornless and
XX sex-reversal. This mutation affects the expression of a transcription factor, FOXL2, inducing an
ectopic expression of this gene in hornbuds (resulting in hornless), while it is repressed in XX
gonads, leading to testis differentiation (XX male). PIS mutation consists in an 11.7kb deletion of
putative regulatory regions located at 300kb upstream of FOXL2. Other genes of this locus, coding
for long ncRNAs, which expression is always correlated with the one of FOXL2, are also misregulated
in PIS+/- or PIS-/- goats. Among them, two are well characterized PISRT1 that is close to the PIS
region and PFOXic expressed from FOXL2 bidirectional promoter; but recent data demonstrated
existence of transcriptional activity in a 100kb area encompassing the PIS region. Interestingly
depending on FOXL2- expressing tissues examined (mutant hornbuds or ovaries), two distinct regions
showed expression of long ncRNAs. These ncRNAs were expressed from one or both strands, suggesting
multiple transcription start sites. It appears that their transcription could be a prerequisite to
FOXL2 expression. Chromatin structure of this ncRNAs containing area was evaluated, comparing
ovary, XY testis, XX testis or liver. Differential epigenetic marks have been observed and will be
presented in regards to the transcriptional activity of this region. In particular, in XX testis
where PIS region is deleted and ncRNAs transcription repressed, active marks co-existed with
repressive marks (like in bivalent domains), while only active marks have been detected in ovary
where ncRNA are transcribed. The existence of a direct link between ncRNAs expression, chromatin
conformation and long-range regulation of FOXL2 gene is hypothesized and should be determined.