WEHI Wednesday Seminar hosted by Dr Hamish King

Gabrielle White
PhD Student – King Laboratory – Molecular Sciences division

(This is a PhD Completion Seminar)

Defining the gene regulatory mechanisms of an immune-specific chromatin reader

Davis Auditorium

Join via SLIDO enter code #WEHIWednesday

Including Q&A session

Speckled Protein 140 (SP140) is a chromatin reader belonging to the Speckled Protein family, named for their localisation to promyelocytic leukaemia nuclear speckles. While most chromatin-associated regulators are ubiquitously expressed across all cell types and tissues, SP140 has a highly specific expression pattern in cells of the immune system, especially B cells. Despite this, and genetic evidence that SP140 is linked to B cell-mediated diseases, it remains poorly understood how SP140 interacts with chromatin to control gene expression in B cells. To investigate this, we profiled the genome-wide binding sites of SP140 in human B cells using CUT&Tag and found that SP140 ubiquitously binds thousands of active and repressed gene promoters. Unexpectedly, we found that SP140 occupancy at gene promoters is closely linked to the absence of DNA methylation, and this binding of SP140 depends upon the KNWR motif within the SP140 SAND domain. In the absence of SP140, we identified widespread transcriptional activation in human B cells, consistent with SP140 maintaining a repressed state at its target gene promoters. These findings establish SP140 as a methylation-sensitive chromatin reader involved in gene repression and provides a foundation for future work into SP140 dysfunction in B cell mediated diseases. 

Gabrielle completed a Bachelor of Biomedical Science at Deakin University, followed by Honours at Peter MacCallum Cancer Centre with Melbourne University, focusing on the molecular foundations of Oral Squamous Cell Carcinoma. She joined the King Lab in 2022 as a Research Assistant and began her PhD in 2023. During this time, she has been the WESA LGBTQIA+ representative, an active member of the WEPRIDE and Reconciliation committees and is a founding member of the Melbourne Epigenetics Club. As a scientist, Gabrielle has a strong interest in chromatin structure and regulation, particularly how disruption of chromatin regulators influences disease.

All welcome!