During differentiation of pluripotent stem cells to cardiomyocytes, the three-dimensional folding of the DNA reorganizes itself. This reorganization of the DNA architecture precedes and defines important epigenetic patterns according to a team of researchers who published their work in Nature Communications.. The results suggest that the genome's spatial organization is an important switch for defining cell types, thereby representing a very promising starting point for future reprogramming strategies.
The genome stores information about an organisms development. Each cell carries this information tightly packed on a two-meter long DNA strand in the cell nucleus and specific epigenetic mechanisms control access to the 'blueprint of life'. Because every cell type in a mammalian organism requires access to genomic areas in a tempo-spatial specific manner, the epigenome is crucial for determining cellular identity.
It is already known that various epigenetic mechanisms are associated with cell differentiation. Particularly indispensable is the methylation of DNA, in which methyl groups are attached to specific nucleotides of double-stranded DNA. Recent studies also show that differentiation processes are accompanied by a reorganization of the three-dimensional folding of the DNA. Up until now, however, it has been unclear what comes first during cardiomyocyte differentiation: the reorganization of the DNA's folding in the cellular nucleus or the DNA's methylation - and whether these mechanisms are dependent on one another.
In order to address this question, the team used modern sequencing methods. These made it possible to map the three-dimensional genome organization as well as epigenetic mechanisms during the differentiation of cardiomyocytes across the entire genome.
For this purpose, the researchers established methods for isolating cardiomyocytes in various developmental stages from healthy mouse hearts. This cell-type-specific analysis was essential to demonstrate that there is a close interplay between epigenetic mechanisms and the spatial folding of the DNA in the cardiomyocytes' nucleus.
The comparison of different stages of development showed that the type of spatial folding of DNA defines which methylation patterns are formed and which genes are activated. The researchers proved that the spatial arrangement of the DNA is not dependent on the DNA methylation with cells, among other things, that have no DNA methylation at all.
The three-dimensional genome organization is thus a central switchboard for determining cellular identity. In the future, the researchers want to use this switch to control cellular functions.
https://www.pr.uni-freiburg.de/pm-en/2017/the-main-switch?set_language=en
http://dx.doi.org/10.1038/s41467-017-01724-9
Three dimensional organization of DNA determines cell type differentiation!
- 2,130 views
- Added
Edited
Latest News
Abusive drugs hijack natura…
By newseditor
Posted 23 Apr
Mechanism of action of the…
By newseditor
Posted 23 Apr
Role of fat in rare neurolo…
By newseditor
Posted 23 Apr
How protein synthesis in de…
By newseditor
Posted 22 Apr
Atlas of mRNA variants in d…
By newseditor
Posted 22 Apr
Other Top Stories
Bone fracture healing requires nerve signaling pathway
Read more
Predicting a protein's behavior from its appearance
Read more
Sensing light without forming images
Read more
Slowing down anxiety with 'Safety signals'
Read more
A key protein linked to ageing identified
Read more
Protocols
A programmable targeted pro…
By newseditor
Posted 23 Apr
MemPrep, a new technology f…
By newseditor
Posted 08 Apr
A tangible method to assess…
By newseditor
Posted 08 Apr
Stem cell-derived vessels-o…
By newseditor
Posted 06 Apr
Single-cell biclustering fo…
By newseditor
Posted 01 Apr
Publications
Exploiting pancreatic cance…
By newseditor
Posted 23 Apr
Structure of antiviral drug…
By newseditor
Posted 23 Apr
Type-I-interferon-responsiv…
By newseditor
Posted 23 Apr
Selenium, diabetes, and the…
By newseditor
Posted 23 Apr
Long-term neuropsychologica…
By newseditor
Posted 23 Apr
Presentations
Hydrogels in Drug Delivery
By newseditor
Posted 12 Apr
Lipids
By newseditor
Posted 31 Dec
Cell biology of carbohydrat…
By newseditor
Posted 29 Nov
RNA interference (RNAi)
By newseditor
Posted 23 Oct
RNA structure and functions
By newseditor
Posted 19 Oct
Posters
A chemical biology/modular…
By newseditor
Posted 22 Aug
Single-molecule covalent ma…
By newseditor
Posted 04 Jul
ASCO-2020-HEALTH SERVICES R…
By newseditor
Posted 23 Mar
ASCO-2020-HEAD AND NECK CANCER
By newseditor
Posted 23 Mar
ASCO-2020-GENITOURINARY CAN…
By newseditor
Posted 23 Mar