"Linker Histones in Stem Cells and Cancer"
Yuhong Fan, PhD
Associate Professor and Georgia Cancer Coalition Distinguished Scholar
Georgia Institute of Technology
Chromatin and epigenetic regulation contribute fundamentally to all cellular processes in normal and disease states. However, the role of higher order chromatin compaction in these processes has not been well explored. H1 linker histones are major chromatin architectural proteins that facilitate the folding of chromatin into higher order structures. Using molecular, cellular, genomic, and mouse genetics approaches, we identify critical roles of linker histone H1 in regulating embryonic stem cell (ESC) pluripotency and differentiation. Through high-resolution mapping, we integrate the localization of H1 variants into the ESC epigenome and uncover novel roles of H1 in pericentric heterochromatin and genome organization in ESCs. On the other hand, by analyzing H1 variants in ovarian cancer cells and H1 mutants present in follicular lymphomas, we establish H1 variants as biomarkers for ovarian cancer, identify H1.3 as a specific and potent repressor for the non-coding oncogenic RNA H19 in ovarian cancer cells, and characterize the H1 mutants in follicular lymphomas as most likely loss-of-function mutants. Taken together, our work elucidates the function and regulatory mechanisms of H1 in stem cells and cancer and suggests modulating H1 variants as a potential new strategy for stem cell therapeutics and cancer treatments.