Can chromatin conformation technologies bring light into human molecular pathology?

• Authors: Marta Kubiak , Marzena Lewandowska
• Languages of publication: EN

Abstracts

EN

Regulation of gene expression in eukaryotes involves many complex processes, in which chromatin structure plays an important role. In addition to the epigenetic effects, such as DNA methylation and phosphorylation or histone modifications, gene expression is also controlled by the spatial organization of chromatin. For example, distant regulatory elements (enhancers, insulators) may come into direct physical interaction with target genes or other regulatory elements located in genomic regions of up to several hundred kilobases in size. Such long-range interactions result in the formation of chromatin loops. In the last several years, there has been a rapid increase in our knowledge of the spatial organization of chromatin in the nucleus through the chromosome conformation capture (3C) technology. Here we review and compare the original 3C and 3C-based methods including chromosome conformation capture-on-chip (4C), chromosome conformation capture carbon copy (5C), hi-resolution chromosome confomation capture (HiC). In this article, we discuss different aspects of how the nuclear organization of chromatin is associated with gene expression regulation and how this knowledge is useful in translational medicine and clinical applications. We demonstrate that the knowledge of the chromatin 3D organization may help understand the mechanisms of gene expression regulation of genes involved in the development of human diseases, such as CFTR (responsible for cystic fibrosis) or IGFBP3 (associated with breast cancer pathogenesis). Additionally, 3C-derivative methods have been also useful in the diagnosis of some leukemia subtypes.

Keywords

EN

chromosome conformation capture; human molecular pathology; chromatin; chromatin looping; genome organization

• Publisher: Polish Biochemical Society
• Journal: Acta Biochimica Polonica
• Year: 2015
• Volume: 62
• Issue: 3
• Pages: 483-489

Dates

published

2015

received

2015-02-03

revised

2015-07-21

accepted

2015-08-04

(unknown)

2015-09-02

Contributors

author

Marta Kubiak

• Molecular Oncology and Genetics Department, Innovative Medical Forum, The F. Lukaszczyk Oncology Center, Bydgoszcz, Poland

author

Marzena Lewandowska

• Molecular Oncology and Genetics Department, Innovative Medical Forum, The F. Lukaszczyk Oncology Center, Bydgoszcz, Poland
• Department of Thoracic Surgery and Tumors, Collegium Medicum, Nicolaus Copernicus University, Bydgoszcz, Poland

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Identifiers

DOI

10.18388/abp.2015_984