We use complementary genetic and epigenetic approaches in mouse models, in order to discover genetic variants in noncoding regions of the genome underlying the etiologies of Tet1-dependent neurulation disorders, or the epigenetic dysregulation related to non-genetic factors, or the combination of both. Studies using transgenic mouse strains generated in the laboratory will be complemented with in vitro studies using mouse and human pluripotent stem cell cultures. Bulk and single-cell multiomics approaches will be used to investigate epigenetic mechanisms regulating chromatin accessibility, gene expression and DNA methylation in neurulation and cell fate reprogramming.
Luo X, van der Veer BK, Sun L, Bartoccetti M, Boretto M, Vankelecom H, Khoueiry R. Koh KP (2020). Coordination of germ-layer lineage choice by TET1 during primed pluripotency. Genes & Development 34(7-8), 598-618.
Bartoccetti M, van der Veer BK, Luo X, Khoueiry R, She P, Bajaj M, Xu J, Janiszewski A, Thienpont B, Pasque V and Koh KP (2020). Regulatory dynamics of Tet1 and Oct4 resolve stages of global DNA demethylation and transcriptomic changes in pluripotency. Cell Reports 30(7), 2150-2169.
Khoueiry R, Sohni A, Thienpont B, Luo XL, Vande Velde J, Bartoccetti M, Boeck B, Zwijsen A, Rao A, Lambrechts D, Koh KP (2017). Lineage-specific functions of TET1 in the post-implantation mouse embryo. Nature Genetics 49, 1061-1072.
Koh KP, Yabuuchi A, Rao S, Huang Y, Cunniff K, Nardone J, Laiho A, Tahiliani M, Sommer CA, Mostoslavsky G, Lahesmaa R, Orkin SH, Rodig SJ, Daley GQ, Rao A (2011). Tet1 and Tet2 regulate 5-hydroxymethylcytosine production and cell lineage specification in mouse embryonic stem cells. Cell Stem Cell 8, 200-213.
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