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• W1675370509 abstract "Friend of GATA-1 (FOG-1) is a member of the friend of GATA (FOG) family of proteins, which consists of large multitype zinc finger cofactors that bind to the amino zinc finger of GATA transcription factors and modulate their activity. FOG-1 also interacts with the C-terminal binding protein (CtBP), mainly known as a corepressor and the nucleosome remodelling and histone deacetylase repressive (NuRD) complex ; thus, integrating FOG-1 into the transcription factor and chromatin modifier networks. Remarkably, the protein activates or represses gene transcription by facilitating binding of GATA factors to DNA, recruiting chromatin remodelling complexes, or by stabilizing tissue-specific chromatin loops. Physical interaction between FOG and GATA proteins in vivo is essential for the development of a broad array of tissues, reflecting the overlapping expression patterns of these factors. Notably, within the haematopoietic system, FOG-1 is absent in most of the myeloid lineages ; it is expressed at high level in multipotent progenitors, erythroid and megakaryocytic cells, low level in lymphoid and haematopoietic stem cells. The cofactor is essential for differentiation of the erythroid and megakaryocytic lineages, notably by interacting with GATA-1. FOG-1 also plays a role in the T-lineage by repressing GATA-3 dependent induction of Th2 development. Interestingly, overexpression of FOG-1 in avian eosinophils, which do not normally express FOG-1, reprograms these differentiated cells into multipotent cells. To study FOG-1 in mammals, we used a novel transgenic mouse model strategy which we had designed to generate mice with conditional overexpression of FOG-1. Our work with enforced expression of FOG-1 in the whole murine haematopoietic system led to a reduction in the number of circulating eosinophils, confirming and extending to mammals the previously reported role of FOG-1 in repressing this lineage development. Strikingly, we have identified the expression of FOG-1 in early B lymphocytes, but not in late developmental stages such as mature B cells and plasma cells. Moreover, FOG-1 function had never been described in the B-lineage, where GATA factors are not expressed. Therefore, we were intrigued by both the regulated expression of FOG-1 during B cell development and its molecular mechanism of action in the absence of GATA factors. Thus, we generated transgenic mice in which FOG-1 expression was enforced at a physiologically relevant level in the B lymphoid system : in mature B cells and from early B cell stages. We found that sustained FOG-1 expression in mature and late B cells did not affect their development or function, contrary to our expected hypothesis. Although the mice overexpressing FOG-1 from early B cell lineages showed only a weak phenotype, we extensively studied FOG-1 partners in early B cell stages. Indeed, describing FOG-1 molecular mechanism of action in the absence of GATA factors is a question that warrant further investigation. We notably found FOG-1 in complex with Ikaros, a transcription factor well described as crucial for B cell development. The cofactor was also found associated to the CtBP and NuRD epigenetic complexes in B cell lines." @default.
• W1675370509 created "2016-06-24" @default.
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• W1675370509 date "2013-01-01" @default.
• W1675370509 modified "2023-09-26" @default.
• W1675370509 title "FOG-1, a transcriptional regulator within the haematopoietic system" @default.
• W1675370509 doi "https://doi.org/10.5451/unibas-006228293" @default.
• W1675370509 hasPublicationYear "2013" @default.
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