Journal
NATURE
Volume 541, Issue 7636, Pages 237-+Publisher
NATURE RESEARCH
DOI: 10.1038/nature20781
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Funding
- Walter V. and Idun Berry Postdoctoral Fellowship
- National Institutes of Health (NIH) Predoctoral Molecular Biophysics Training Program
- National Science Foundation Graduate Fellowship
- National Institutes of Health (NIH) [R01GM106005]
- NIH [R21HG007726, P50HG00773501]
- Rita Allen Foundation
- Baxter Foundation
- Human Frontier Science Program
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Chromatin structure at the length scale encompassing local nucleosome-nucleosome interactions is thought to play a crucial role in regulating transcription and access to DNA(1-3). However, this secondary structure of chromatin remains poorly understood compared with the primary structure of single nucleosomes or the tertiary structure of long-range looping interactions(4). Here we report the first genome-wide map of chromatin conformation in human cells at the 1-3 nucleosome (50-500 bp) scale, obtained using ionizing radiation-induced spatially correlated cleavage of DNA with sequencing (RICC-seq) to identify DNA-DNA contacts that are spatially proximal. Unbiased analysis of RICC-seq signal reveals regional enrichment of DNA fragments characteristic of alternating rather than adjacent nucleosome interactions in tri-nucleosome units, particularly in H3K9me3-marked heterochromatin. We infer differences in the likelihood of nucleosome-nucleosome contacts among open chromatin, H3K27me3-marked, and H3K9me3-marked repressed chromatin regions. After calibrating RICC-seq signal to three-dimensional distances, we show that compact two-start helical fibre structures with stacked alternating nucleosomes are consistent with RICC-seq fragmentation patterns from H3K9me3-marked chromatin, while non-compact structures and solenoid structures are consistent with open chromatin. Our data support a model of chromatin architecture in intact interphase nuclei consistent with variable longitudinal compaction of two-start helical fibres.
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