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Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1.

ABSTRACT: Transcriptional regulation of ESR1, the gene that encodes for estrogen receptor α (ER), is critical for regulating the downstream effects of the estrogen signaling pathway in breast cancer such as cell growth. ESR1 is a large and complex gene that is regulated by multiple regulatory elements, which has complicated our understanding of how ESR1 expression is controlled in the context of breast cancer. Early studies characterized the genomic structure of ESR1 with subsequent studies focused on identifying intrinsic (chromatin environment, transcription factors, signaling pathways) and extrinsic (tumor microenvironment, secreted factors) mechanisms that impact ESR1 gene expression. Currently, the introduction of genomic sequencing platforms and additional genome-wide technologies has provided additional insight on how chromatin structures may coordinate with these intrinsic and extrinsic mechanisms to regulate ESR1 expression. Understanding these interactions will allow us to have a clearer understanding of how ESR1 expression is regulated and eventually provide clues on how to influence its regulation with potential treatments. In this review, we highlight key studies concerning the genomic structure of ESR1, mechanisms that affect the dynamics of ESR1 expression, and considerations towards affecting ESR1 expression and hormone responsiveness in breast cancer.

SUBMITTER: Lung DK

PROVIDER: S-EPMC7384552 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Overhunting typically increases during and after armed conflicts, and may lead to regional-scale defaunation. The mitigation of hunting impacts is complex because, among other reasons, several intrinsic and extrinsic motivations underpin the elevated deployment of hunting practices. Here we present the first study focusing on these motivations in a post-war zone. Following persistently heavy hunting pressure during the 27-year Angolan civil war, the offtake of small to medium-bodied species has increased recently as a result of large mammal depletion. However, prey choice associated with different motivations varied in terms of species trophic level and body size. While most residents hunted large-bodied species to maximize revenues from wildlife trade, many low-trophic level smaller species were harvested to meet local subsistence demands because they were more palatable and could be captured using artisanal traps near hunters' households. Mainly low-trophic level species were killed in retaliation for crop-raiding or livestock depredation. Considering all game species sampled in this study, 96% were captured to attend two or more motivations. In addition, hunting associated with different motivations was partitioned in terms of age and gender, with prey acquisition for the wildlife trade primarily carried out by adult men, while hunting to meet local subsistence needs and inhibit human-wildlife conflicts were carried out by adult men and women, children and even the elderly. In natural savannah areas lacking fish as a source of protein, a higher number of species was selected to supply both the meat trade and subsistence, while more species in forest areas were targeted for trade in animal body parts and conflict retaliation. Finally, local commerce in bushmeat and other body parts accrued higher domestic revenues compared to any alternative sources of direct and indirect income. However, these financial benefits were at best modest, largely unsustainable in terms of prey population collapses, and generated high long-term costs for the local to regional scale economy and native biodiversity.

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Intrinsic and Extrinsic Factors Governing the Transcriptional Regulation of ESR1.

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