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- W3175339440 abstract "PU.1 (encoded by Spi1), an ETS-family transcription factor with many hematopoietic roles, is highly expressed in the earliest intrathymic T cell progenitors but must be down-regulated during T lineage commitment. The transcription factors Runx1 and GATA3 have been implicated in this Spi1 repression, but the basis of the timing was unknown. We show that increasing Runx1 and/or GATA3 down-regulates Spi1 expression in pro-T cells, while deletion of these factors after Spi1 down-regulation reactivates its expression. Leveraging the stage specificities of repression and transcription factor binding revealed an unconventional but functional site in Spi1 intron 2. Acute Cas9-mediated deletion or disruption of the Runx and GATA motifs in this element reactivates silenced Spi1 expression in a pro-T cell line, substantially more than disruption of other candidate elements, and counteracts the repression of Spi1 in primary pro-T cells during commitment. Thus, Runx1 and GATA3 work stage specifically through an intronic silencing element in mouse Spi1 to control strength and maintenance of Spi1 repression during T lineage commitment." @default.
- W3175339440 created "2021-07-05" @default.
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- W3175339440 date "2021-06-28" @default.
- W3175339440 modified "2023-10-16" @default.
- W3175339440 title "Stage-specific action of Runx1 and GATA3 controls silencing of PU.1 expression in mouse pro–T cells" @default.
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- W3175339440 doi "https://doi.org/10.1084/jem.20202648" @default.
- W3175339440 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8241539" @default.
- W3175339440 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34180951" @default.
- W3175339440 hasPublicationYear "2021" @default.
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