Biology subjects

Cammas, F. M.

Publications and source records attributed to Cammas, F. M..

2 recordsLinked to original sources

bioRxiv2021

TRIM28-dependent SUMOylation protects the adult ovary from the male pathway

Gonadal sexual fate in mammals is determined during embryonic development and must be actively maintained in adulthood. In the mouse ovary, oestrogen receptors and FOXL2 protect ovarian granulosa cells from transdifferentiation into Sertoli cells, their testicular counterpart. However, the mechanism underlying their protective effect is unknown. Here, we show that TRIM28 is required to prevent female-to-male sex reversal of the mouse ovary after birth. We found that upon loss of Trim28, ovarian granulosa cells transdifferentiate to Sertoli cells through an intermediate cell type, different from gonadal embryonic progenitors. TRIM28 is recruited on chromatin in the proximity of FOXL2 to maintain the ovarian pathway and to repress testicular-specific genes. The role of TRIM28 in ovarian maintenance depends on its E3-SUMO ligase activity that regulates the sex-specific SUMOylation profile of ovarian-specific genes. Our study identifies TRIM28 as a key factor in protecting the adult ovary from the testicular pathway.

developmental biology↗

bioRxiv2018

The mouse HP1 proteins are not required for cell viability but are essential for preventing liver tumorigenesis

Chromatin organization plays essential roles in cell identity and functions. Here, we demonstrated by hepatocyte-specific inactivation of the genes encoding the three Heterochromatin Protein 1 (HP1, {beta} and {gamma}) in mice (HP1-TKO) that these proteins are dispensable for hepatocyte activity and survival. Conversely, the chronic absence of these proteins led to a drastic increased incidence of liver tumor development. Molecular characterization of HP1-TKO hepatocytes revealed that HP1 proteins are required for maintenance of histone marks associated with heterochromatin, and for the appropriate expression of large number of genes involved in liver-specific functions as well as in genes encoding for transcriptional repressors of the KRAB-ZFP family. Moreover, several specific endogenous retrovirus families were upregulated in HP1-TKO hepatocytes, leading to the deregulated expression of genes in their vicinity. Our findings indicate that HP1 proteins act as guardians of liver homeostasis to prevent tumor development through the modulation of multiple chromatin-associated events.

cancer biology↗