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Mapping out genome wide binding sites of Prox1 by CUT&RUN approach in mouse cochlea

ABSTRACT: Mapping out genome wide binding sites of Prox1 by CUT&RUN approach in mouse cochlea

PROVIDER: PRJNA609690 | ENA |

REPOSITORIES: ENA

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Mapping out genome wide binding sites of Prox1 by CUT&RUN approach in mouse cochlea

Project description:The homeobox transcription factor Prox1 is critical for organogenesis including brain, retina, liver and pancreas and lymphatic system. Prox1 is transiently expressed in mouse cochlear hair cells (HCs) and supporting cells (SCs), however, it remains elusive about its in vivo DNA binding site and roles during cochlear development. Here, by using fresh cochlear tissues and Prox1 antibody, we firstly mapped out the genome-wide binding sites of Prox1 via Cleavage Under Targets and Release Using Nuclease (CUT&RUN). Gene function enrichment analysis suggests several potential functions of Prox1, one of which is regulating cell cycle progression. Secondly, to validate our CUT&RUN data, we further performed in vivo prox1 gain-of-function studies through genetic approaches. Onset of ectopic Prox1 at early embryonic otocyst leads to shorter cochlea with density of HCs and SCs distribution, suggesting a precocious cell cycle exit of cochlear sensory progenitor cells. These findings highlight the power of CUT&RUN in mapping DNA binding sites even in tissues (i.e. cochlea) with rare cells, as well as providing the first genetic evidence to support roles of Prox1 in regulating progenitor pools of cochlear progenitors.

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