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Variable chromatin structure revealed by in situ spatially correlated DNA cleavage mapping

机译：可变染色质结构通过原位空间相关的DNA裂解作图揭示

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摘要

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.
机译：染色质结构的长度范围涵盖局部核小体-核小体相互作用，被认为在调节转录和对DNA的访问中起着至关重要的作用（1-3）。然而，与单核小体的一级结构或长距离环化相互作用的三级结构相比，染色质的这种二级结构仍然知之甚少（4）。在这里我们报告了人类细胞中1-3个核小体（50-500 bp）规模上染色质构象的第一个全基因组全图，该图是使用电离辐射诱导的DNA空间相关切割与测序（RICC-seq）鉴定DNA获得的-DNA接触在空间上是近端的。 RICC-seq信号的无偏分析揭示了在三核小体单元中，特别是在H3K9me3标记的异染色质中，交替而不是相邻核小体相互作用的特征性DNA片段区域富集。我们推断在开放染色质，H3K27me3标记和H3K9me3标记的压抑染色质区域之间核小体与核小体接触的可能性的差异。在将RICC-seq信号校准到三维距离后，我们显示具有堆叠交替的核小体的紧凑型两起点螺旋纤维结构与H3K9me3标记的染色质的RICC-seq片段化模式一致，而非紧凑型结构和螺线管结构一致与开放的染色质。我们的数据支持完整相间核中染色质体系结构的模型，该模型与双起始螺旋纤维的可变纵向压实一致。

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  • 来源
    《Nature》 |2017年第7636期|237-241|共5页
  • 作者

    Risca Viviana I.; Denny Sarah K.; Straight Aaron F.; Greenleaf William J. .;

  • 作者单位

    Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA;

    Stanford Univ, Biophys Program, Stanford, CA 94305 USA;

    Stanford Univ, Dept Biochem, Sch Med, Stanford, CA 94305 USA|Stanford Univ, Sch Med, Dept Chem & Syst Biol, Stanford, CA 94305 USA;

    Stanford Univ, Dept Genet, Sch Med, Stanford, CA 94305 USA|Stanford Univ, Biophys Program, Stanford, CA 94305 USA|Stanford Univ, Dept Appl Phys, Sch Med, Stanford, CA 94305 USA;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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