Scientists have identified a protein called RSF1 that plays a role in the mechanisms that turn sets of genes on or off. This work comes from the University of Alabama at Birmingham and was published this week in Proceedings of the National Academy of Sciences.
In his current work, Hengbin Wang, an associate professor of biochemistry and molecular genetics at the UAB School of Medicine, focused on the addition of ubiquitin to the histone subunit H2A. The modification is linked to gene silencing, and removal of ubiquitin from H2A leads to gene activation. The protein that mediates the gene-silencing function of ubiquitinated-H2A is RSF1.
They found that RSF1 is a ubiquitinated-H2A binding protein that reads ubiquitinated-H2A through a previously uncharacterized and obligatory ubiquitinated-H2A binding domain. In human and mouse cells, the genes regulated by RSF1 were found to overlap significantly with those controlled by the part of a complex that ubiquitinates H2A. When RSF1 was knocked out, they found that the genes regulated by RSF1 were no longer silenced, and this was accompanied by changes in ubiquitinated-H2A chromatin organization and release of linker histone H1.
"RSF1 binds to ubiquitinated-H2A nucleosomes to establish and maintain the stable ubiquitinated-H2A nucleosome pattern at promoter regions. The stable nucleosome array leads to a chromatin architecture that is refractory to further remodeling required for ubiquitinated-H2A target gene activation. When RSF1 is knocked out, ubiquitinated-H2A nucleosome patterns are disturbed and nucleosomes become less stable, despite the presence of ubiquitinated-H2A. These ubiquitinated-H2A nucleosomes are subjected to chromatin remodeling for gene activation," researchers wrote in the paper.
Wang says knowledge of the ubiquitinated-H2A binding site may help in the discovery of other ubiquitinated histone-binding proteins.
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