Chromatin Conformation Signatures: Ideal Human Disease Biomarkers?

Abstract

Human health is related to information stored in our genetic code, which is highly variable even amongst healthy individuals. Gene expression is orchestrated by numerous control elements that may be located anywhere in the genome, and can regulate distal genes by physically interacting with them. These DNA contacts can be mapped with the chromosome conformation capture and related technologies. Several studies now demonstrate that gene expression patterns are associated with specific chromatin structures, and may therefore correlate with chromatin conformation signatures. Here, we present an overview of genome organization and its relationship with gene expression. We also summarize how chromatin conformation signatures can be identified and discuss why they might represent ideal biomarkers of human disease in such genetically diverse populations.

Spatial Organization of Epigenomes

“…In this respect, chromatin organization is often altered in human diseases such as cancer [102], and we have recently provided evidence of its value as a discovery tool for candidate cancer biomarkers [103]. It will be interesting to see whether chromatin conformations actually represent ideal biomarkers and to define the value of such signatures in the clinic [104]. …”

Detecting DNA–Protein Interactions in Living Cells—ChIP Approach

“…Therefore, these technologies yield averaged structural models, rather than true structures. Although these models can be noisy, they remain useful to identify changes between cell states (Crutchley, Wang, Ferraiuolo, & Dostie, 2010). When analyzing data from 3C-based methods, one should bear in mind that, although functionally significant long-range contacts may occur between regulatory elements and target genes, other long-range interactions may simply be a consequence of genome compaction and bear no immediately apparent functional significance.…”

“…Depending on the way 3C fragments are analyzed, Chromatin Conformation Capture on chip (4C), Chromatin Conformation Capture Carbon Copy (5C), Combined Chromatin Conformation Capture ChIP cloning (6C), and Hi-C have been developed (reviewed in details in Crutchley et al, 2010).…”

Epigenetic regulation of retinal development and disease

“…Thus, acetylation/deacetylation regulatory mechanisms can have broader target ranges than just histone proteins. Rhodopsin Euchromatin CTs III Activation/abnormal nuclear architecture -SCA7, RB [92,110] RD retinal degeneration, SCA7 spinocerebellar ataxia type 7, RB retinoblastoma, CTs chromatin territories j ocul biol dis inform (2011) 4: [121][122][123][124][125][126][127][128][129][130][131][132][133][134][135][136]Higher-order chromosomal organizations and transcription…”

“…These assays take a snapshot of the 3D organization of chromatin architecture of chemically fixed cells/tissues. This 3D organization includes long-range physical contacts between DNA sequences located in the same (cis) or on different (trans) chromosomes (for reviews see [132,133]). These techniques combined with three-dimensional multi-color DNA/RNA fluoresence in situ hybridization (FISH) [134,135] and electron microscopic techniques allow visualization of intra-and inter-chromosome loops and chromatin territories within the individual nucleus (nuclear compartmentalization) [136].…”