The linker histone (H1) family is a fundamental component of chromatin that is critical for the higher order compaction of the eukaryotic genome, and thus a key player in the regulation of all DNA-templated processes. While the exact mechanism of H1 compaction has been investigated both in vitro and in vivo, noticeable gaps persist, primarily due to a lack of molecular tools. Specifically, all human H1 variants have never been purified and biochemically characterized. Here we describe a broadly applicable strategy to purify linker histones and demonstrate its utility by purifying all somatic H1 variants as well as one germline variant. Using this library of linker histones, we performed a first ever direct biochemical comparison and discovered a gradient of compaction abilities and nucleosome binding affinities. This data offers new insight into H1 redundancy and provides a starting point for further investigation of H1 mutations that drive disease.

Robust method for the purification and characterization of human histone H1 variants

2019 Spring National Meeting

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