Counting Eight Breakthroughs of Hi-C Technology in 2018

2018 is destined to be an extraordinary year, regardless of the birth of somatic cloned monkeys Zhongzhong and Huahua, or the discovery of ancient mixed races, or the superconductivity of graphene magic angle to improve energy efficiencygreatly, which will eventually be remembered by history as wonderful moments. In the field of biology, gene editing, precision medicine, high-throughput sequencing and other words that used to appear only in textbooks are now coming into our life. In this year, Hi-C technology, the hot topic in the field of high-throughput sequencing, has continued to harvest many “first articles”. By convention, we will present an annual inventory of Anno’s exclusive Hi-C classic articles for everyone, and see what they have.

In Medical Research Field

April, 2018, providing a systematic perspective for the role of enhancers in a variety of cancers for the first time

May, 2018, integrating Hi-C, eQTL, and epigenome annotation data to explore the occurrence of osteoporosis

August, 2018, deciphering the 3D structure of human diploid single-cell genome successfully for the first time

In Animal Research Field

July, 2018, revealing the three-dimensional genomic characteristics of zebrafish for the first time

July, 2018, the first three-dimensional structure analysis of Peking duck genome (cooperate with Annoroad)

In Plant Research Field

April, 2018, further analysis of the fine structure characteristics of rice chromatin (cooperate with Annoroad)

November, 2018, obtaining the reference genome of andrographis chromosome level (cooperate with Annoroad)

In Microbiology Research Field

October, 2018, the first interaction research between virus and host Hi-C

A pan-cancer analysis of enhancer expression in nearly 9,000 patient samples[1]

Published in: Cell (IF=31.398)

Using the RNA-seq data of the TCGA database, 33 types of cancer and 8,928 patient samples were found, and the characteristics of a large number of active enhancers in the whole genome were analyzed. It was found that the tumor tissue has broader enhancer activity. Integrating CNV and mutation data, it was found that the activation of tumor tissue enhancers was positively correlated with tumor aneuploidy, but not related to point mutations or slightly negatively correlated. This is because aneuploidy leads to chromatin opening, resulting in enhancer activation (ATAC-seq). Integrating eQTL and Hi-C data, to test the interaction between enhancers and genes, revealing the effective genes in clinical, and further identify the enhancer of 140kb downstream of pd-l1. This study provides a systematic view of the role of enhancers in a variety of cancers and explains the potential clinical implications of enhancers.


An osteoporosis risk snp at 1p36.12 acts as an allele-specific enhancer to modulate LINC00339 expression via long-range loop formation[2]

Published inAmerican Journal of Human GeneticsIF=8.855

By integrating Hi-C, eQTL, and epigenetic annotation data, combined with dual luciferase and CRISPR/Cas9 multiple functional verification experiments, it was finally confirmed that the rs6426749-SNP site of the 1p36.12 region regulates the expression of long-chain non-coding RNA (LINC00339) located outside ~360 kb by CTCF-mediated chromatin looping. LINC00339 negatively regulates CDC42, reducing the number of transcripts, which affects the proliferation and differentiation of osteoblasts, leading to the occurrence of osteoporosis.


Three-dimensional genome structures of single diploid human cells[3]

Published in: Science (IF=41.058)

The 3D structure of diploid cells has not been deciphered. The main reason is that the 23 chromosomes from the female parent are almost indistinguishable from the 23 chromosomes from the male parent. Professor Xie Xiaoliang’s Harvard team used the Dip-C method to obtain the 3D structure of a single diploid human cell genome for the first time, and found systematic differences in different cell types. This is a new method of structural biology for the nucleus and will have important applications in many fields of biomedicine.


Systemic loss and gain of chromatin architecture throughout zebrafish development[4]

Published in: Cell ReportsIF=8.032

The Hi-C map during zebrafish embryo development was described for the first time. The zebrafish genome and mammalian genome have similar TAD and A/B compartments structural features. The TAD structure was established prior to the formation of the 2.25 hpf zygote, transcription has not yet occurred at this time. The TAD intensity was significantly reduced during the 4 hpf period and then established again. And in the phase of the disappearance of the compartment and TAD, the super-enhancer interaction still exists, which indicates that the super-enhancer interaction does not depend on the TAD and A/B compartments structure.


An intercross population study reveals genes associated with body size and plumage color in ducks[5]Article in collaboration with Annoroad

Published in: Nature CommunicationsIF=12.353

This study analyzed the regulatory mechanisms of two key traits of Peking duck feather color and body shape. The study found that due to the insertion of a large 6.6kb sequence into the MITF gene, the transcription responsible for melanin synthesis was completely suppressed, and the melanin synthesis pathway was shut down, thus forming the white feathers of Peking duck. At the same time, due to a natural mutation of the remote enhancer, the IGF2BP1 gene, which plays a role in promoting growth during the embryonic period, continues to be expressed after the Peking duck has broken the shell, which improves the efficiency of feed utilization and thus becomes larger. In order to avoid the error of remote-control analysis caused by genome assembly errors, the authors verified the heat map of the end region of chr28 by Hi-C data, and found that the assembly effect was good, and there was no obvious large-scale fragment inversion.


Genome-wide Hi-C analysis reveals extensive hierarchical chromatin interactions in rice[6]Article in collaboration with Annoroad

Published in: Plant JournalIF=5.775


In this paper, the 3d structure of rice chromosome was analyzed comprehensively, and the characteristics of compartment A/B and local domains were confirmed. Furthermore, the detailed structure characteristics of rice chromatin were analyzed, including chromatin loops, self-looped gene, IHI/KEEs and FIREs. The results of the paper provide powerful data and theoretical references for further exploration of the molecular mechanisms of rice and other cereal crops.


The medicinal plant Andrographis paniculata genome provides insight into biosynthesis of the bioactive diterpenoid neoandrographolide[7]Article in collaboration with Annoroad

Published inPlant JournalIF=5.775

The study combined with three generations and Hi-C assisted assembly technology to obtain the reference genome of Andrographis 269M in high-quality chromosome level, AnnoGene involved in Hi-C assisted assembly work, contigs mount rate of more than 95%.

The study revealed the synthesis mechanism of the bioactive material diterpene lactone new andrographolide through the assembly of the Andrographis genome.


Tridimensional infiltration of DNA viruses into the host genome shows preferential contact with active chromatin[8]

Published inNature CommunicationsIF=12.353

The Hi-C technology was used to study the changes of chromosome three-dimensional structure of human hepatoma cells after HBV and Ad5 infection for the first time. HBV infection cannot change the three-dimensional structure of the host chromosome, while Ad5 infection can change the three-dimensional structure of the host chromosome. HBV tends to bind to the CpG island region rich in cytokine Cfp1; Ad5 is more likely to interact with TSSs and enhancers. These characteristics of the virus targeting specific regions are actually beneficial to their own replication and transcription.


It can be seen from the above that Hi-C technology has a wide range of applications in the fields of medicine, animal, plant and microbiology. These studies usually use Hi-C as the lead for genomic three-dimensional spatial structure research, combined with ATAC-seq, ChIP-seq, RNA-seq and other multi-omics data for joint analysis, and multiple omics mutual verification complement each other. This forms a complete chain of evidence, which enables an in-depth analysis of the mechanism of gene expression regulation. With this perfect “key”, will high-scoring articles be far behind?

2019 has arrived, and the editor believes that we will eventually move forward. The road to scientific research is long, I hope everyone has a light in the heart, there is a way at the foot, AnnoGene will always accompany you!


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