Distinct Structures and Dynamics of Chromatosomes with Different Human Linker Histone Isoforms

Author:

Zhou, Bing-Rui

Feng, Hanqiao

Kale, Seyit

Fox,Tara

Khant,Htet

De Val Alda,Natalia

Ghirlando, Rodolfo

Panchenko, Anna R

Bai, Yawen
Author Address

Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA., Izmir Biomedicine and Genome Center, Dokuz Eylul University Health Campus, Balcova, Izmir 35330, Turkey., Center of Macromolecular Microscopy, National Cancer Institute, Cancer Research Technology Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21701, USA., Laboratory of Molecular Biology, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA., Department of Pathology and Molecular Medicine, School of Medicine, Queen 39;s University, Kingston, ON K7L 3N6, Canada., Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA. Electronic address: baiyaw@mail.nih.gov.,

Abstract:

The repeating structural unit of metazoan chromatin is the chromatosome, a nucleosome bound to a linker histone, H1. There are 11 human H1 isoforms with diverse cellular functions, but how they interact with the nucleosome remains elusive. Here, we determined the cryoelectron microscopy (cryo-EM) structures of chromatosomes containing 197 bp DNA and three different human H1 isoforms, respectively. The globular domains of all three H1 isoforms bound to the nucleosome dyad. However, the flanking/linker DNAs displayed substantial distinct dynamic conformations. Nuclear magnetic resonance (NMR) and H1 tail-swapping cryo-EM experiments revealed that the C-terminal tails of the H1 isoforms mainly controlled the flanking DNA orientations. We also observed partial ordering of the core histone H2A C-terminal and H3 N-terminal tails in the chromatosomes. Our results provide insights into the structures and dynamics of the chromatosomes and have implications for the structure and function of chromatin. Published by Elsevier Inc.

See More

Author Address