The role of aberrant transcription factor expression and loss of epigenetic control in activating long-terminal-repeats in Hodgkin’s lymphoma

Edginton-White, Benjamin (2018). The role of aberrant transcription factor expression and loss of epigenetic control in activating long-terminal-repeats in Hodgkin’s lymphoma. University of Birmingham. Ph.D.

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Abstract

Long terminal repeat (LTR) elements are wide-spread in the human genome and have the potential to act as alternative promoters and enhancers. Their expression is therefore under tight epigenetic control. We previously reported that a member of a specific class ofLTR elements (THE I B) in Hodgkin's Lymphoma (HL) acted as a promoter for the growth factor receptor gene CSF 1 R and that this gene is required for HL cell survival. However, to which extent and how such elements participate in shaping the unique gene expression program of HL is unknown. To address this question we mapped the genome-wide activation ofLTRs in HL using a novel targeted next generation sequencing approach (RACE-Seq). Integration of such data with global gene expression as well as chromatin profiling data from HL and non-HL cell lines discovered a unique pattern of LTR activation impacting on gene expression, including a number of genes associated with the HL phenotype. We also show that global LTR activation is induced by activation of inflammatory signaling pathways. Together these results demonstrate that LTR activation presents an additional layer of gene expression deregulation in HL and highlight the potential for the impact of genome-wide L TR activation in other inflammatory diseases.

Type of Work:

Thesis (Doctorates > Ph.D.)

Award Type:

Doctorates > Ph.D.

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