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- W3182109425 abstract "Abstract The evolution of uniquely human traits likely entailed changes in developmental gene regulation. Human Accelerated Regions (HARs), which include transcriptional enhancers harboring a significant excess of human-specific sequence changes, are leading candidates for driving gene regulatory modifications in human development. However, insight into whether HARs alter the level, distribution and timing of endogenous gene expression remains limited. We examined the role of the HAR HACNS1 (HAR2) in human evolution by interrogating its molecular functions in a humanized mouse model. We find that HACNS1 maintains its human-specific enhancer activity in humanized mice and that it modifies expression of Gbx2 , which encodes a homeobox transcription factor, during limb development. Using single-cell RNA-sequencing, we demonstrate that Gbx2 is upregulated in the chondrogenic mesenchyme of humanized limbs, supporting that HACNS1 alters gene expression in cell types involved in skeletal patterning. Our findings illustrate that humanized mouse models provide mechanistic insight into how HARs modified gene expression in human evolution." @default.
- W3182109425 created "2021-07-19" @default.
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- W3182109425 date "2019-12-12" @default.
- W3182109425 modified "2023-09-25" @default.
- W3182109425 title "Modeling uniquely human gene regulatory function in humanized mice" @default.
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- W3182109425 doi "https://doi.org/10.1101/2019.12.11.873075" @default.
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