The Chromatin-looping Factor ZNF143 is Genetically Altered and Promotes the Oestrogen Response in Breast Cancer
Year: 2016
Type: dissertation
Abstract: Oestrogen signalling in breast cancer (BrCa) cells relies on chromatin-loops that connect distal regulatory elements bound by the oestrogen receptor 1 (ESR1) to target gene promoters. We show that chromatin-looping factor genes, including CTCF, ZNF143 and RAD21, are genetically altered in BrCa. Expanding on the function of CTCF and cohesin in BrCa, we demonstrate that ZNF143 binds promoters of most early-response oestrogen target genes connected to distal regulatory elements in ESR1-positive BrCa cells. Its chromatin occupancy is unaffected by oestrogen-stimulation, supporting a stable three-dimensional genomic architecture within the oestrogen response. Its loss abrogates the oestrogen-induced transcriptional response and growth of BrCa cells. Furthermore, we show that the overexpression of looping-factors within ESR-1 positive BrCa patients associates with a worse clinical outcome. Overall, our results suggest that ZNF143 is a new critical effector of the oestrogen response and highlights the contribution of the chromatin looping machinery to ESR1-positive BrCa development.
Source: TSpace (University of Toronto)
Author: Aislinn E. Treloar
Language: English
Subfield: Endocrinology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2561095837