Structure of Native Chromatin Fibres Revealed by Cryo-ET in situ

Abstract

The structure of chromatin plays pivotal roles in regulating gene transcription, DNA replication and repair, and chromosome segregation. This structure, however, remains elusive. Using cryo-FIB and cryo-ET, we delineated the 3D architecture of native chromatin fibres in intact interphase human T-lymphoblasts and determined the in-situ structures of nucleosomes in different conformations. These chromatin fibres are not structured as uniform 30 nm one-start or two-start filaments but are composed of relaxed, variable zigzag organizations of nucleosomes connected by straight linker DNA. Nucleosomes with little H1 and linker DNA density were distributed randomly without any spatial preference. This work sets a precedent for future high-resolution investigations on native chromatin structures in-situ at both a single-nucleosome level and a population level under many different cellular conditions in health and disease.