Search bioRxiv⌕ Search

Biology subjects

Roper, E. A.

Publications and source records attributed to Roper, E. A..

2 recordsLinked to original sources

Maternal SMCHD1 controls both imprinted Xist expression and imprinted X chromosome inactivation

Embryonic development is dependent on the maternal supply of proteins through the oocyte, including factors setting up the adequate epigenetic patterning of the zygotic genome. We previously reported that one such factor is the epigenetic repressor SMCHD1, whose maternal supply controls autosomal imprinted expression in mouse preimplantation embryos and mid-gestation placenta. In mouse preimplantation embryos, X chromosome inactivation is also an imprinted process. Combining genomics and imaging, we show that maternal SMCHD1 is required not only for the imprinted expression of Xist in preimplantation embryos, but also for the efficient silencing of the inactive X in both the preimplantation embryo and mid-gestation placenta. These results expand the role of SMCHD1 in enforcing the silencing of Polycomb targets. The inability of zygotic SMCHD1 to fully restore imprinted X inactivation further points to maternal SMCHD1s role in setting up the appropriate chromatin environment during preimplantation development, a critical window of epigenetic remodelling.

genomics↗

SINEultaneous profiling of epigenetic heterogeneity and transcriptome in single cells

Global changes in DNA methylation are observed in developmental and disease contexts, and singlecell analyses are highlighting the heterogeneous regulation of these processes. However, technical challenges associated with single-cell analysis of DNA methylation limit these studies. We present single-cell transposable element methylation sequencing (scTEM-seq) for cost-effective estimation of global DNA methylation levels. By targeting high-copy LINE-1 and SINE Alu elements, we achieve amplicon bisulphite sequencing with thousands of loci covered in each library. Parallel transcriptome analysis is also performed to link global DNA methylation heterogeneity with gene expression. We apply scTEM-seq to KG1a acute myeloid leukaemia (AML) cells, and primary AML cells. Decitabine treatment of KG1a cells induces global DNA methylation heterogeneity associated with altered expression of immune process genes. We also compare global levels of DNA methylation to expression of transposable elements and find a predominance of negative correlations in both the KG1a and patient cells. Finally, we observe co-ordinated upregulation of many transposable elements in a sub-set of decitabine treated cells. By linking global DNA methylation heterogeneity with transcription, scTEM-seq will refine our understanding of epigenetic regulation in cancer and beyond.

genomics↗