Deciphering Hi-C: from 3D genome to function

Kong, Siyuan; Zhang, Yubo

doi:10.1007/s10565-018-09456-2

Cited by 62 publications

(47 citation statements)

References 113 publications

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“…Phenotypic changes induced by microgravity mainly involve epigenetic modifications, since only very few single nucleotide polymorphisms (SNPs) and small insertions and deletions (Indels) occur (Aunins et al, 2018;Tirumalai et al, 2019). As an important content of epigenetics, genome conformation is associated with gene expression and varies with the surroundings (Kong and Zhang, 2019). In this study, high aspect-ratio rotating-wall vessels (HARVs) were used to create the SMG conditions (Tryggvason et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Changes in Vibrio natriegens Growth Under Simulated Microgravity

Yin¹,

Jin³

et al. 2020

Front. Microbiol.

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The growth rate of bacteria increases under simulated microgravity (SMG) with lowshear force. The next-generation microbial chassis Vibrio natriegens (V. natriegens) is a fast-growing Gram-negative, non-pathogenic bacterium with a generation time of less than 10 min. Screening of a V. natriegens strain with faster growth rate was attempted by 2-week continuous long-term culturing under SMG. However, the rapid growth rate of this strain made it difficult to obtain the desired mutant strain with even more rapid growth. Thus, a mutant with slower growth rate emerged. Multi-omics integration analysis was conducted to explore why this mutant grew more slowly, which might inform us about the molecular mechanisms of rapid growth of V. natriegens instead. The transcriptome data revealed that whereas genes related to mechanical signal transduction and flagellin biogenesis were up-regulated, those involved in adaptive responses, anaerobic and nitrogen metabolism, chromosome segregation and cell vitality were down-regulated. Moreover, genome-wide chromosome conformation capture (Hi-C) results of the slower growth mutant and wide type indicated that SMG-induced great changes of genome 3D organization were highly correlated with differentially expressed genes (DEGs). Meanwhile, whole genome re-sequencing found a significant number of structure variations (SVs) were enriched in regions with lower interaction frequency and down-regulated genes in the slower growth mutant compared with wild type (WT), which might represent a prophage region. Additionally, there was also a decreased interaction frequency in regions associated with well-orchestrated chromosomes replication. These results suggested that SMG might regulate local gene expression by sensing stress changes through conformation changes in the genome region of genes involved in flagellin, adaptability and chromosome segregation, thus followed by alteration of some physiological characteristics and affecting the growth rate and metabolic capacity.

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Section: Introductionmentioning

confidence: 99%

Changes in Vibrio natriegens Growth Under Simulated Microgravity

Yin¹,

Jin³

et al. 2020

Front. Microbiol.

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“…Hi-C captures regions of the genome that are physically interacting, and can be covalently connected by a cross-linking agent 27 . The hg38 reference genome was digitally digested with MboI, DpnII and HindIII to obtain all possible Hi-C fragment locations for the 90 PD-SNP loci.…”

Section: Codes3d Integrates Data On Spatial Interactions Between Genomic Loci (Hi-c Data;mentioning

confidence: 99%

Establishing gene regulatory networks from Parkinson’s disease risk loci

Farrow

Schierding

Gokuladhas

et al. 2021

Preprint

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The latest meta-analysis of genome wide association studies (GWAS) identified 90 independent single nucleotide polymorphisms (SNPs) across 78 genomic regions associated with Parkinson's disease (PD), yet the mechanisms by which these variants influence the development of the disease remains largely elusive. To establish the functional gene regulatory networks associated with PD-SNPs, we utilised an approach combining spatial (chromosomal conformation capture) and functional (expression quantitative trait loci; eQTL) data. We identified 518 genes subject to regulation by 76 PD-SNPs across 49 tissues, that encompass 36 peripheral and 13 CNS tissues. Notably, one third of these genes were regulated via trans- acting mechanisms (distal; risk locus-gene separated by > 1Mb, or on different chromosomes). Of particular interest is the identification of a novel trans-eQTL-gene connection between rs10847864 and SYNJ1 in the adult brain cortex, highlighting a convergence between familial studies and PD GWAS loci for SYNJ1 (PARK20) for the first time. Furthermore, we identified 16 neuro-development specific eQTL-gene regulatory connections within the foetal cortex, consistent with hypotheses suggesting a neurodevelopmental involvement in the pathogenesis of PD. Through utilising Louvain clustering we extracted nine significant and highly intra-connected clusters within the entire gene regulatory network. The nine clusters are enriched for specific biological processes and pathways, some of which have not previously been associated with PD. Together, our results not only contribute to an overall understanding of the mechanisms and impact of specific combinations of PD-SNPs, but also highlight the potential impact gene regulatory networks may have when elucidating aetiological subtypes of PD.

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“…Recently, the Hi-C in situ chromosome conformation capture technique has been applied to test for a chromatin architectural role for RNA. Hi-C captures 3-D interactions by ligating proximal genomic regions and can be combined with in situ RNase digestion to probe the effect of total RNA depletion on genome organization [52]. Hi-C of control cells detected genomic compartments (compartment A corresponding to euchromatin and compartment B corresponding to heterochromatin) which are further subdivided into distinct long-range topologically associated domains (TADs) that define the set of interactions within a given region [41,53].…”

Section: Evidence For Structural Roles Of Rna In Chromatin Organizationmentioning

confidence: 99%

Architectural RNA in chromatin organization

Thakur

Henikoff

2020

Biochemical Society Transactions

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RNA plays a well-established architectural role in the formation of membraneless interchromatin nuclear bodies. However, a less well-known role of RNA is in organizing chromatin, whereby specific RNAs have been found to recruit chromatin modifier proteins. Whether or not RNA can act as an architectural molecule for chromatin remains unclear, partly because dissecting the architectural role of RNA from its regulatory role remains challenging. Studies that have addressed RNA's architectural role in chromatin organization rely on in situ RNA depletion using Ribonuclease A (RNase A) and suggest that RNA plays a major direct architectural role in chromatin organization. In this review, we will discuss these findings, candidate chromatin architectural long non-coding RNAs and possible mechanisms by which RNA, along with RNA binding proteins might be mediating chromatin organization.

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Deciphering Hi-C: from 3D genome to function

Cited by 62 publications

References 113 publications

Changes in Vibrio natriegens Growth Under Simulated Microgravity

Changes in Vibrio natriegens Growth Under Simulated Microgravity

Establishing gene regulatory networks from Parkinson’s disease risk loci

Architectural RNA in chromatin organization

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