Biology subjects

Mjoseng, H. K.

Publications and source records attributed to Mjoseng, H. K..

2 recordsLinked to original sources

bioRxiv2019

DNA methylation directs polycomb-dependent 3D genome re- organisation in naive pluripotency

The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naive pluripotency by culturing in 2i conditions results in redistribution of polycomb (H3K27me3) away from its target loci. Here we demonstrate that 3D genome organisation is also altered in 2i. We found chromatin decompaction at polycomb target loci as well as loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground-state, we are able to restore the H3K27me3 distribution, and polycomb-mediated 3D genome organisation that is characteristic of primed ESCs grown in serum, to ESCs in 2i. However, these cells retain the functional characteristics of 2i ground state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organisation but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs.

cell biology↗

bioRxiv2017

A reassessment of DNA immunoprecipitation-based genomic profiling

DNA immunoprecipitation sequencing (DIP-seq) is a common enrichment method for profiling DNA modifications in mammalian genomes. However, DIP-seq profiles often exhibit significant variation between independent studies of the same genome and from profiles obtained by alternative methods. Here we show that these differences are primarily due to intrinsic affinity of IgG for short unmodified DNA repeats. This pervasive experimental error accounts for 50 - 99% of regions identified as enriched for DNA modifications in DIP-seq data. Correction of this error profoundly alters DNA modification profiles for numerous cell types, including mouse embryonic stem cells, and subsequently reveals novel associations between DNA modifications, chromatin modifications and biological processes. We propose new methodological guidelines that minimize the impact of these errors on future DIP-seq experiments and allow new insights to be made from the wealth of existing DIP-seq data.

genetics↗