UC Riverside

Histone chaperones are important molecular players that help decide the when and how of cellular identity. Many studies have revealed these proteins have roles in forming chromatin structure, via interaction with histones and nucleosomes, and are important regulators of different molecular pathways involved with cell fate decisions. However, these proteins are multifunctional and, given their importance, there are still many unknown aspects of the relationships between histone chaperones and how different cellular contexts may be affected by histone chaperone processes. Two important histone chaperones CAF-1 and SPT6 have interesting roles in the maintenance of chromatin during replication and transcription, respectively. In addition, they have been shown to be very important players in maintaining cell identity through chromatin assembly and through regulation of other pathways. For example, we have previously shown that the replication dependent histone chaperone CAF-1 is a critical regulator of myeloid progenitors and participates in heterochromatin formation. Using an RNAi screen, we also show that, among histone chaperones, SPT6 is a top regulator. Here, using functional cell assays and genomic sequencing methods, we investigated how disruption of CAF-1 and SPT6 affects cellular identity. Overall, we established these histone chaperones as important maintainers of cellular identity and show how CAF-1 and SPT6 can have divergent roles in chromatin maintenance that have both unique and common implications and consequences for cell identity.