Bioinformatics Seminar
Time: 11AM
Venue: Davis Auditorium and Online
7 November 2023
Investigating the impact of Kap1 loss on chromatin organisation of mammary epithelia using single-cell multiome data
Malindrie DharmaratneWEHI ACRF Cancer Biology and Stem Cells/Bioinformatics
The structure of chromatin determines gene expression and subsequently cell fate. Our collaborators have recently characterised the chromatin structure of the mouse mammary gland, revealing stark differences in distinct lineages within the epithelium that regulate their chromatin and gene expression. Kap1 (aka Trim28, Tif1β) is a master regulator of chromatin, controlling heterochromatin formation and influencing histone acetylation, methylation and ubiquitination. Furthermore, Kap1 is critical in regulating cellular differentiation, DNA repair and metastasis. We hypothesise that Kap1 is a key regulator of the mammary epigenome and understanding how Kap1 regulates mammary cells will be critical in understanding genome organisation during oncogenesis. To study the impact of Kap1 loss on the epigenome and transcriptome of mammary epithelial cells, our collaborators have generated paired multiome data from Kap1 knockout and wild-type mice. In this talk, I will discuss the differences in how basal, luminal progenitor, and mature luminal cells regulate their genome in the presence of Kap1 loss. Furthermore, I will discuss the computational pipeline I utilized to analyse multiome data, highlighting some of the challenges with respect to data analysis, specifically in doublet detection, peak calling, integration, and normalization of multiome data.