Characterisation of innate immune gene activities in rested and stimulated states
AuthorHuang, Edward Cheng-Ta
AffiliationAnatomy and Neuroscience
Document TypePhD thesis
Access StatusThis item is embargoed and will be available on 2020-08-29.
© 2018 Dr Edward Cheng-Ta Huang
Monocytes and macrophages are among the first line of response to an infectious agent. The quality of this response will influence the type of T-lymphocyte recruited and may determine the outcome of an infection. While much is known about the repertoire of genes expressed by monocytes and macrophages in response to an acute challenge, little is known about the potential to diversify these responses through the generation of transcript isoforms. The role of transcriptional complexity in determining immune responses to stimulation has not been previously addressed in primary human monocytes. Transcriptional complexity is a measure of the abundance and diversity of transcript isoforms expressed in a genome. It has previously been demonstrated on a few genes in human myeloid cells that transcript isoforms can be expressed in a stimulus-specific manner and play important roles in immune responses. Although the expression of different transcript isoforms has been previously evaluated through the study of alternate splicing, the contribution of alternate transcription start sites has not been systematically addressed. We used CAGE-seq and ATAC-seq to characterise the extent of altering transcription start site usage following exposing monocytes to different stimuli. The comparison of the differences in alternate transcription start site usage between monocytes and macrophages revealed that these two cell types have a similar repertoire of transcription start sites. However, the transcriptional complexity focuses were different in these two cell types. Monocytes displayed dynamic changes in the alternate transcription start site usage in response to distinct stimuli, suggesting its plastic roles in immune responses. Although the mechanisms underlying the transcription start site selection have not been determined in this study, we proposed a model that differential recruitment of transcription factors to distinct promoters was predicted to initiate transcription from different transcription start sites. We have identified the potential transcription factors that were used to select transcription start sites in different conditions. The better understanding of the transcriptional complexity in primary human monocytes will assist gaining better insight into the involvement of monocytes in immune responses.
Keywordstranscription; innate immunity; monocytes; macrophages; transcriptional complexity; miRNA; transcription start sites
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