Conventional and unconventional interactions of the transcription factor FOXL2 uncovered by a proteome‐wide analysis

Abstract

Beyond the study of its transcriptional target genes, the identification of the various interactors of a transcription factor (TF) is crucial to understand its diverse cellular roles. We focused on FOXL2, a winged‐helix forkhead TF important for ovarian development and maintenance. FOXL2 has been implicated in diverse cellular processes, including apoptosis, the control of cell cycle or the regulation of steroid hormone synthesis. To reliably identify partners of endogenous FOXL2, we performed a proteome‐wide analysis using co‐immunoprecipitation in the murine granulosa cell‐derived AT29c and the pituitary‐derived alpha‐T3 cell lines, using three antibodies targeting different parts of the protein. Following a stringent selection of mass spectrometry data on the basis of identification reliability and protein enrichment, we identified a core set of 255 partners common to both cell lines. Their analysis showed that we could co‐precipitate several complexes involved in mRNA processing, chromatin remodeling and DNA replication and repair. We further validated (direct and/or indirect) interactions with selected partners, suggesting an unexpected role for FOXL2 in those processes. Overall, this comprehensive analysis of the endogenous FOXL2 interactome sheds light on its numerous and diverse interactors and unconventional cellular roles.

TRIM28-dependent SUMOylation protects the adult ovary from activation of the testicular pathway

“…3F, right). These results are supported by a previous proteomic analysis of murine granulosa and pituitary-derived cell lines showing that TRIM28 and FOXL2 are engaged in common protein complexes 24 . Overall, the previous data on FOXL2 4 and our results show that in the ovary, TRIM28 and FOXL2 are implicated in the same genetic pathway to maintain the ovarian cell fate.…”

Gene Variant of Barrier to Autointegration Factor 2 (Banf2w) Is Concordant with Female Determination in Cichlids

“…Interaction between Banf1 and Banf2 occurs through formation of homo-and hetero-dimers, which is especially important in testis [64]. Banf1 is a repressor of foxl2's pro-apoptotic activity [66,67] and is involved with gonad development [64,68]. Thus, acting in chromatin assembly, the nuclear-lamina-associated Banf1 protein may indirectly impact granulosa cell differentiation and apoptosis [66,67].…”

“…Banf1 is a repressor of foxl2's pro-apoptotic activity [66,67] and is involved with gonad development [64,68]. Thus, acting in chromatin assembly, the nuclear-lamina-associated Banf1 protein may indirectly impact granulosa cell differentiation and apoptosis [66,67]. Bound to emerin complexes in the nuclear envelope [69], Banf1 may repress foxl2 by mediating its relocation to the nuclear periphery [67].…”

Immunoprecipitation and mass spectrometry define TET1 interactome during oligodendrocyte differentiation

“…Subsequently, to remove potential contaminants, we used the CRAPmoe database [ 19 ], which contains a compilation of proteins frequently identified in affinity purification MS control. We considered that any proteins in our data with a CRAPome max spectral count over 200 (1.99% genes in OPC and 1.77% in OL) or the multiplication for the number of experiments and max spectral count over 100 were contaminants [ 20 ]. This step identified a total of 54 contaminants.…”