The Role of High-Order Chromatin Organization in Gene Regulation

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Background

The regulation of gene expression in eukaryotes is controlled by many factors, among which the composition and spatial organization of chromatin are extremely important.

Firstly, local chromatin environments define DNA accessibility for transcription factors and RNA polymerases. Secondly, high-order chromatin organization determines the spatial proximity between different DNA regulatory elements (such as promoters, enhancers, etc.) as well as their radial nuclear positioning that either stimulate or repress gene activity. For example, topologically associated domains (TADs) were revealed in the majority of studied eukaryotic cell types by chromatin capture methods, such as Hi-C. TADs can be generally divided into A and B types, which primarily correspond to active and repressed chromatin states. Cell type-specific borders of TADs correlate well with the gene expression programs. Although some particular DNA sequences and proteins were identified to contribute to chromatin looping and TAD formation, the detailed mechanisms controlling positions of TAD borders as well as long-range interactions between individual TADs are still not fully understood.

Another type of high-order chromatin organization is represented by lamina-associated domains (LADs) that were originally identified via DNA adenine methyltransferase identification and Chromatin immunoprecipitation approaches. Like TADs, LADs were also identified in a wide range of species, from yeast and plants to mammals including humans. LADs consist of genomic sequences with a very low transcriptional activity that is located at the periphery of the nucleus. Almost the same sequences were found to be also enriched at the periphery of the nucleolus (in the so-called nucleolus associated domains or NADs). Apparently, these sequences shuffle from LADs to NADs and vice-versa during cell divisions. The interactions of chromosomal fragments with the nuclear lamina and the periphery of the nucleolus are also cell-type specific and appear to be crucial for proper gene expression. In addition, the single-cell studies revealed a stochastic component in forming TADs and LADs. Finally, a growing amount of evidence suggests that impairment of high-order chromatin structure is associated with different pathological states, such as cancer, metabolic disorders and laminopathies.

In this Research Topic, we aim to gather Original Research and Review Article papers on novel aspects of the involvement of high-order chromatin organization in the regulation of gene expression in eukaryotes. Brief Reports, Mini-Reviews are welcomed too. Potential topics include, but are not limited to the following:
• Cell type-specific and tissue-specific organization and functioning of high-order chromatin domains;
• Dynamics of spatio-temporal organization of chromatin during development, cell differentiation and aging;
• Impairments of the 3D chromatin architecture leading to pathological states;
• Technological advances to assess spatial chromatin configuration and function.

Keywords: high-order chromatin organization, gene regulation, TADs, LADs, NADs, eukaryotes

Important note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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