| Chromosome structure plays important roles in many aspects of genome regulations in eukaryotes, such as gene expression, DNA replication and maintenance of genome stability. Chromatin interaction is always a vital part of chromosome structure. Currently, there are two types of approaches are being used to study chromosome structure. The first category is to study chromosome structure and chromatin dynamics in single cells with microscopic methods, like FISH. Secondly, approaches based on the Chromosome Conformation Capture technology (3C) allow to obtain information on average chromatin folding for large populations of cells.3C technology is mainly used to study physical interaction between regulatory DNA elements and distant target genes, and it has now become a standard research tool for studying the relationship between nuclear organization and transcription in the native cellular state.3C technology has a high resolution in the range of several Kb, significantly higher than achievable by light microscopy. A series of 3C-based technologies have been developed, including 4C,5C, Hi-C and ChLA-PET. All the current high-throughput technologies are affected both by technical biases, including those from sequencing and mapping, and biological biases, such as those resulting from intrinsic physical properties of distinct chromatin states. Hi-C technology allows to study the dynamic chromatin interactions across the entire genome. But it is in the range of more than 10 Kb, which is not accurate enough to study regulatory elements. So precision 3C data are still very import to build a high-revolution interactions model of distant gene regulatory elements. Therefore, we developed a database of 3C (3CDB; http://3cdb.big.ac.cn), which contains all the published 3C data. To build 3CDB, we searched PubMed and Google Scholar with carefully designed keyword combinations and retrieved more than 6000 papers, we subsequently manually extracted 3319 interactions in 157 species. With the development of 3C technology, its experiment protocols and standards have changed, then it is unable to compare 3C contact frequencies between different experiments. To solve this problem, we proposed a systematic evaluation scheme for data reliability and classified the interactions into four categories. We believe 3C data in the same categories would be comparable.In the microevolutionary process of cancer cells, the nuclear organization structure would be significant changes. However, chromatin conformation changes have not been well studied in this process. In our research, we study one aspect of the chromatin conformation changes, nucleosome array changes, during experimental evolution of a human breast (MCF10A) cell-derived xenograft in mice. The experimental evolution of xenograft tumour in mice is a common model for the tumor microevolution. We obtained Mnase-seq and RNA-seq data of experimental evolution of a MCF10A cell-derived xenograft tumour in mice from He, Xionglei’s lab in Sun Yat-sen University. With CISD (Chromatin Interaction Site Detector), a new tool developed in our lab, we detected nucleosome array distribution changes. We found that there is a correlation between MSD segments (Merged Segments with significant Difference) and expressed genome regions. And there is also a correlation between expressed genome regions and the length of MSD segments. There are more long MSD segments enrichment in gene regions with expression. Maybe long MSD segments has different nucleosome array models with short MSD segments. It still need to explore the relation between MSD segments and tissue-specific genes. |
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