Dataset Information

Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.

ABSTRACT: The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by the boundaries of topologically associating domains (TADs), demonstrating the role of the 3D genome structure in modulating the spatial distribution of RNA. Conversely, stopping transcription or acute depletion of RNA induces thousands of chromatin loops genome-wide. Activation or suppression of the transcription of specific genes suppresses or creates chromatin loops straddling these genes. Deletion of a specific caRNA-producing genomic sequence promotes chromatin loops that straddle the interchromosomal target sequences of this caRNA. These data suggest a feedback loop where the 3D genome modulates the spatial distribution of RNA, which in turn affects the dynamic 3D genome organization.

SUBMITTER: Calandrelli R

PROVIDER: S-EPMC10579264 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.

Calandrelli Riccardo R Wen Xingzhao X Charles Richard John Lalith JL Luo Zhifei Z Nguyen Tri C TC Chen Chien-Ju CJ Qi Zhijie Z Xue Shuanghong S Chen Weizhong W Yan Zhangming Z Wu Weixin W Zaleta-Rivera Kathia K Hu Rong R Yu Miao M Wang Yuchuan Y Li Wenbo W Ma Jian J Ren Bing B Zhong Sheng S

Nature communications 20231016 1

The interphase genome is dynamically organized in the nucleus and decorated with chromatin-associated RNA (caRNA). It remains unclear whether the genome architecture modulates the spatial distribution of caRNA and vice versa. Here, we generate a resource of genome-wide RNA-DNA and DNA-DNA contact maps in human cells. These maps reveal the chromosomal domains demarcated by locally transcribed RNA, hereafter termed RNA-defined chromosomal domains. Further, the spreading of caRNA is constrained by ...[more]

PMID: 37845234

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Project description:BackgroundOur appreciation of the critical role of the genome's 3D organization in gene regulation is steadily increasing. Recent 3C-based deep sequencing techniques elucidated a hierarchy of structures that underlie the spatial organization of the genome in the nucleus. At the top of this hierarchical organization are chromosomal territories and the megabase-scale A/B compartments that correlate with transcriptional activity within cells. Below them are the relatively cell-type-invariant topologically associated domains (TADs), characterized by high frequency of physical contacts between loci within the same TAD, and are assumed to function as regulatory units. Within TADs, chromatin loops bring enhancers and target promoters to close spatial proximity. Yet, we still have only rudimentary understanding how differences in chromatin organization between different cell types affect cell-type-specific gene expression programs that are executed under basal and challenged conditions.ResultsHere, we carried out a large-scale meta-analysis that integrated Hi-C data from thirteen different cell lines and dozens of ChIP-seq and RNA-seq datasets measured on these cells, either under basal conditions or after treatment. Pairwise comparisons between cell lines demonstrate a strong association between modulation of A/B compartmentalization, differential gene expression and transcription factor (TF) binding events. Furthermore, integrating the analysis of transcriptomes of different cell lines in response to various challenges, we show that A/B compartmentalization of cells under basal conditions significantly correlates not only with gene expression programs and TF binding profiles that are active under the basal condition but also with those induced in response to treatment. Yet, in pairwise comparisons between different cell lines, we find that a large portion of differential TF binding and gene induction events occur in genomic loci assigned to A compartment in both cell types, underscoring the role of additional critical factors in determining cell-type-specific transcriptional programs.ConclusionsOur results further indicate the role of dynamic genome organization in regulation of differential gene expression between different cell types and the impact of intra-TAD enhancer-promoter interactions that are established under basal conditions on both the basal and treatment-induced gene expression programs.

Dataset Information

Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.

Publications

Genome-wide analysis of the interplay between chromatin-associated RNA and 3D genome organization in human cells.

Similar Datasets

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