Journal article
A Prox1 enhancer represses haematopoiesis in the lymphatic vasculature
J Kazenwadel, P Venugopal, A Oszmiana, J Toubia, L Arriola-Martinez, V Panara, SG Piltz, C Brown, W Ma, AW Schreiber, K Koltowska, S Taoudi, PQ Thomas, HS Scott, NL Harvey
Nature | NATURE PORTFOLIO | Published : 2023
Abstract
Transcriptional enhancer elements are responsible for orchestrating the temporal and spatial control over gene expression that is crucial for programming cell identity during development1–3. Here we describe a novel enhancer element that is important for regulating the expression of Prox1 in lymphatic endothelial cells. This evolutionarily conserved enhancer is bound by key lymphatic transcriptional regulators including GATA2, FOXC2, NFATC1 and PROX1. Genome editing of the enhancer to remove five nucleotides encompassing the GATA2-binding site resulted in perinatal death of homozygous mutant mice due to profound lymphatic vascular defects. Lymphatic endothelial cells in enhancer mutant mice ..
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Awarded by University of Melbourne
Funding Acknowledgements
We thank the staff at the UniSA Core Animal Facility for animal husbandry and D. Lawrence for assistance with initial bioinformatic analyses. This study utilized the Australian Phenomics Network Histopathology and Organ Pathology Service (University of Melbourne) and the South Australian Genome Editing Service (University of Adelaide). Confocal microscopy and flow cytometry were performed at the Detmold Imaging and Flow Cytometry Facility (UniSA). This work was supported by grants from the NHMRC (1061365 and 1146706 to N.L.H. and H.S.S.) and ARC (DP210103351 to N.L.H.). K.K. and V.P. were supported by Wallenberg Fellowships (2017.0144), Vetenskapsadet (VR-MH-2016-01437) and the Kjell and Maerta Beijer Foundation. P.V. was supported by a fellowship from Maddie Riewoldt's Vision (MRV0017). N.L.H. was supported by an ARC Future Fellowship (FT130101254). H.S.S. was supported by an NHMRC Principal Research Fellowship (1023059) and Cancer Council SA's Beat Cancer Project on behalf of its donors and the State Government of South Australia through the Department of Health.