Local and global chromatin interactions are altered by large genomic deletions associated with human brain development

Xianglong Zhang; Ying Zhang; Xiaowei Zhu; Carolin Purmann; Michael S. Haney; Thomas Ward; Arineh Khechaduri; Jie Yao; Sherman M. Weissman; Alexander E. Urban

doi:10.1038/s41467-018-07766-x

Local and global chromatin interactions are altered by large genomic deletions associated with human brain development

Xianglong Zhang, Ying Zhang, Xiaowei Zhu, Carolin Purmann, Michael S. Haney, Thomas Ward, Arineh Khechaduri, Jie Yao, Sherman M. Weissman, Alexander E. Urban^*

^*Corresponding author for this work

Research output: Journal Publications and Reviews › RGC 21 - Publication in refereed journal › peer-review

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Abstract

Large copy number variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. Here we report on the epigenomic effects of the prominent large deletion CNVs on chromosome 22q11.2 and on chromosome 1q21.1. We use Hi-C analysis of long-range chromosome interactions, including haplotype-specific Hi-C analysis, ChIP-Seq analysis of regulatory histone marks, and RNA-Seq analysis of gene expression patterns. We observe changes on all the levels of analysis, within the deletion boundaries, in the deletion flanking regions, along chromosome 22q, and genome wide. We detect gene expression changes as well as pronounced and multilayered effects on chromatin states, chromosome folding and on the topological domains of the chromatin, that emanate from the large CNV locus. These findings suggest basic principles of how such large genomic deletions can alter nuclear organization and affect genomic molecular activity.

Original language	English
Article number	5356
Journal	Nature Communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-07766-x
Publication status	Published - 1 Dec 2018
Externally published	Yes

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title = "Local and global chromatin interactions are altered by large genomic deletions associated with human brain development",

abstract = "Large copy number variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. Here we report on the epigenomic effects of the prominent large deletion CNVs on chromosome 22q11.2 and on chromosome 1q21.1. We use Hi-C analysis of long-range chromosome interactions, including haplotype-specific Hi-C analysis, ChIP-Seq analysis of regulatory histone marks, and RNA-Seq analysis of gene expression patterns. We observe changes on all the levels of analysis, within the deletion boundaries, in the deletion flanking regions, along chromosome 22q, and genome wide. We detect gene expression changes as well as pronounced and multilayered effects on chromatin states, chromosome folding and on the topological domains of the chromatin, that emanate from the large CNV locus. These findings suggest basic principles of how such large genomic deletions can alter nuclear organization and affect genomic molecular activity.",

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AU - Zhang, Xianglong

AU - Zhang, Ying

AU - Zhu, Xiaowei

AU - Purmann, Carolin

AU - Haney, Michael S.

AU - Ward, Thomas

AU - Khechaduri, Arineh

AU - Yao, Jie

AU - Weissman, Sherman M.

AU - Urban, Alexander E.

N1 - Publication details (e.g. title, author(s), publication statuses and dates) are captured on an “AS IS” and “AS AVAILABLE” basis at the time of record harvesting from the data source. Suggestions for further amendments or supplementary information can be sent to [email protected].

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N2 - Large copy number variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. Here we report on the epigenomic effects of the prominent large deletion CNVs on chromosome 22q11.2 and on chromosome 1q21.1. We use Hi-C analysis of long-range chromosome interactions, including haplotype-specific Hi-C analysis, ChIP-Seq analysis of regulatory histone marks, and RNA-Seq analysis of gene expression patterns. We observe changes on all the levels of analysis, within the deletion boundaries, in the deletion flanking regions, along chromosome 22q, and genome wide. We detect gene expression changes as well as pronounced and multilayered effects on chromatin states, chromosome folding and on the topological domains of the chromatin, that emanate from the large CNV locus. These findings suggest basic principles of how such large genomic deletions can alter nuclear organization and affect genomic molecular activity.

AB - Large copy number variants (CNVs) in the human genome are strongly associated with common neurodevelopmental, neuropsychiatric disorders such as schizophrenia and autism. Here we report on the epigenomic effects of the prominent large deletion CNVs on chromosome 22q11.2 and on chromosome 1q21.1. We use Hi-C analysis of long-range chromosome interactions, including haplotype-specific Hi-C analysis, ChIP-Seq analysis of regulatory histone marks, and RNA-Seq analysis of gene expression patterns. We observe changes on all the levels of analysis, within the deletion boundaries, in the deletion flanking regions, along chromosome 22q, and genome wide. We detect gene expression changes as well as pronounced and multilayered effects on chromatin states, chromosome folding and on the topological domains of the chromatin, that emanate from the large CNV locus. These findings suggest basic principles of how such large genomic deletions can alter nuclear organization and affect genomic molecular activity.

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Local and global chromatin interactions are altered by large genomic deletions associated with human brain development

Abstract

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