Essential histone chaperones collaborate to regulate transcription and chromatin integrity [Research Papers]

In this study, we selected for suppressors of a temperature-sensitive spt6 mutation that disrupts the Spt6-Spn1 physical interaction and that also causes both transcription and chromatin defects. This selection identified novel mutations in FACT. Surprisingly, suppression by FACT did not restore the Spt6-Spn1 interaction, based on coimmunoprecipitation, ChIP, and mass spectrometry experiments. Furthermore, suppression by FACT bypassed the complete loss of Spn1. Interestingly, the FACT suppressor mutations cluster along the FACT-nucleosome interface, suggesting that they alter FACT-nucleosome interactions. In agreement with this observation, we showed that the spt6 mutation that disrupts the Spt6-Spn1 interaction caused an elevated level of FACT association with chromatin, while the FACT suppressors reduced the level of FACT-chromatin association, thereby restoring a normal Spt6-FACT balance on chromatin. Taken together, these studies reveal previously unknown regulation between histone chaperones that is critical for their essential in vivo functions.

Source: Genes and Development - May 3, 2021 Category: Genetics & Stem Cells Authors: Viktorovskaya, O., Chuang, J., Jain, D., Reim, N. I., Lopez-Rivera, F., Murawska, M., Spatt, D., Churchman, L. S., Park, P. J., Winston, F. Tags: Research Papers Source Type: research