Role of the telomere binding protein TbUMSBP2 in chromatin remodeling in trypanosomes

DNA replication, maintenance and transcription require the decondensation or “opening” of the condensed DNA to enhance its accessibility to the replication and transcription machineries. The Universal Minicircle Sequence Binding Protein (UMSBP) is a CCHC-type zinc-finger protein that has been previously found to function in the replication and segregation the mitochondrial kinetoplast DNA (kDNA) and to be essential for telomeres stability and integrity. In a previous study we have found that the interactions of mitochondrial UMSBP with kinetoplast-associated histone H1-like proteins (KAPs) resulted in the decondensation of the kDNA network. Here, we have explored the possibility that the nuclear TbUMSBP2 of Trypanosoma brucei may interact with T. brucei nuclear core histones and linker histone H1 and studied the potential consequences of these interactions. Yeast two hybrid, as well as protein-affinity chromatography revealed specific protein-protein interactions between TbUMSBP2 and core histones H2A, H2B H4 and histone H1. Fluorescence microscopy and biochemical analyses demonstrated that these protein-protein interactions resulted in the decondensation of DNA condensed by core these histones. Furthermore, challenging TbUMSBP2 capacity to remodel a complete genome of the metazoan eukaryote Xenopus laevis packed sperm chromatin, has led to remodeling of packed chromatin. UMSBP2 has the potential capacity to function in vivo as chromatin remodeler that renders it accessible to the replication and transcription machineries. These observations demonstrate the remodeling of a condensed kDNA/chromatin via specific interactions of histones with TbUMSBP2, indicate a route for genome remodeling, which may be common to both the mitochondrial and nuclear genomes in trypanosomes.