Elucidating the Regulatory Role of SETDB1 in Epigenome and 3D Chromatin Structures in Melanoma

Abstract

SETDB1 is a histone methyltransferase that catalyzes the deposition of H3K9me3. It functions as a transcriptional suppressor through direct binding at gene promoters and repetitive elements to initiate formation of heterochromatin. Another mechanism of SETDB1-mediated transcription repression is through antagonizing CTCF binding thereby influencing chromatin loops. Unsurprisingly, numerous studies have highlighted the role of SETDB1 in cancer development and progression. Notably, SETDB1 has been identified as an oncogene in melanoma, where its transcriptional overexpression significantly contributes to pathogenesis and correlates with worse prognosis in patients. While progress has been made in understanding several genes and pathways regulated by SETDB1, how SETDB1 functions in driving gene dysregulation through its known mechanisms requires further investigation. In this project, I utilized three melanoma cell lines (Me190, Me260, Me300) with different expression levels of SETDB1 to investigate its impact on histone marks and 3D chromatin architecture. Through analysis of H3K9me3 ChIP-seq and Hi-C data, I aim to characterize the functional role of SETDB1 in shaping the epigenetic landscape and spatial genome organization. Preliminary findings suggest that differential enrichment of H3K9me3 across the genome influences chromatin looping and transcriptional regulation.

Date of Award	2025
Original language	English
Awarding Institution	The Hong Kong University of Science and Technology
Supervisor	Danny Chi Yeu LEUNG (Supervisor)