Quantitative method to study epigenetic landscape of cells
A new method, developed by Banushree Kumar and Simon Elsässer at Karolinska Institutet, produces quantitative maps for modifications of so-called histone proteins that package the DNA molecules in every eukaryotic cell. The study, published in the journal Cell Reports, describes new properties of naïve pluripotent stem cells.
Embryonic stem cells are formed at the earliest stage of organismal life and give rise to all cells of a human body. It is a quest of reparative medicine to understand the biology of this so-called naïve pluripotent cell type that has the potential to generate all other cell types.
The two researchers from Karolinska Institutet’s Department of Medical Biochemistry and Biophysics have developed a new, quantitative, variant of a technique called Chromatin Immunoprecipitation Sequencing (ChIP-Seq) to map modifications of histone proteins that package the DNA molecules. It is believed that these histone modifications encode so-called epigenetic information – information that exists 'on top' of genetic information reflecting the cell's state and identity.
The method uses ‘multiplexing’ to combine many different samples into a single experiment and allows quantitative comparisons between samples. Using barcode information unique to every sample, an algorithm can restore the epigenetic landscapes of each sample from massive parallel DNA sequencing data.
Culturing mouse embryonic stem cells under different conditions, the researchers show how a naïve state is stabilized in mouse embryonic stem cells through the interplay of several histone modifications. The new quantitative methodology and biological insight will also add to our understanding of human pluripotent stem cells and their use in reparative medicine.
This study was financed by the Karolinska Institutet SFO in Molecular Biosciences, Swedish Research Council, the European Union and the Ming Wai Lau Centre for Reparative Medicine.
“Quantitative multiplexed ChIP reveals global alterations that shape promoter bivalency in ground state embryonic stem cells”, Banushree Kumar and Simon J Elsässer, Cell Reports, 17 September 2019, doi: https://doi.org/10.1016/j.celrep.2019.08.046.