Chromatin loops and functions (ImageCRISPR)

All our cells in our body have the same DNA. The difference between cell types is explained by gen expression programmes in our cells. DNA is packaged into a structure called chromatin where genes that are active are positioned in the more open regions whereas genes that are silenced are found in the closed chromatin regions. Although we have long thought that our genes have static positions in the cell, recent discoveries have shown that active genes move and can meet within the nucleus. This communication fine-tunes gene activity or silences genes, however the basic mechanisms are not well understood. To understand the underlying mechanisms of gene regulation we have used public available data and developed techniques to study and characterize the activity and movement of individual genes. We have developed two new labeling methods for individual genes in living cells. Using our newly developed methods in characterizing the mechanisms of gene regulation may gain new knowledge on diseases affecting large proportion of the human population, such as cancer. Our methods will have impact in the field of epigenetics.

I dette prosjektet har me utvikla nye metoder for å følge gen lokus i levande celler ved hjelp av fluoreserande protein og mikroskop. DOFI for ein av metodene blir føld opp vidare gjennom Inven2 og begge metodene vil bli offentleggjort. Dette vil vera nyttig for forskningsfeltet nasjonalt og internasjonalt då desse metodane gjev moglegheit til å få svar på spørsmål om gendynamikk, bevegelse og relasjon til regulatoriske elementer. Prosjektdeltakarane har fått vera med på å skape noko heilt nytt.

In eukaryotes, the genetic information of a cell is packaged into chromatin. The differentiation of embryonic stem cells (ESCs) to all somatic cell types is dependent on changes to gene expression programs defined by the underlying chromatin compaction levels. This proposal uses state of the art methods and will develop an innovative and groundbreaking imaging techniques to study fundamental questions of gene regulation and live-cell chromatin dynamics. Super-resolution imaging creates new possibilities to investigate mechanisms behind chromatin looping and compaction. This project represent a direction of research that goes beyond the now well-established patterns of histone modifications and will have a strong focus on the next level: on the mechanisms of how higher levels of chromatin compaction is controlled. By studying these mechanisms we may gain new knowledge of how genes are regulated in diseases affecting large proportion of the population, such as cancer. Moreover, the two techniques developed will have innovative impact in the field of epigenetics.