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The Hmgn Family of Chromatin Binding Proteins Regulates Stem Cells Pluripotency and Neuronal Differentiation

Hmgn family members are nucleosome-binding proteins that regulate the deposition of histone modifications, compete with linker histones, and interact with several transcription factors. Hmgn1 and Hmgn2 are ubiquitously highly expressed in embryonic tissue, and are progressively downregulated during embryogen-esis. Using RNAi, we have shown that Hmgn proteins are essential for the expression of key pluripotency genes, including Oct4 and Nanog, in embryonal carcinoma cells. This provides a molecular basis for the observations that an Hmgn2 knockout is embryonic lethal, and that manipulating the Hmgn content of early Xenopus embryos causes major developmental defects. We have also shown that Hmgn proteins are very highly expressed in neural stem cells, both during embryogenesis and in the adult mouse brain. We studied the effects of Hmgn knockdown on the neuronal differentiation of embryonal carcinoma cells in vitro. The expression levels of various neural stem cell and neuronal genes were altered following Hmgn knockdown, showing that Hmgn proteins are important for accurate neuronal differentiation and function. We are currently investigating the epigenetic mechanisms underlying these effects on gene expression.