Spatiotemporal role of SETD2-H3K36me3 in murine pancreatic organogenesis.

Pancreas development is tightly controlled by multilayer mechanisms. Despite years of effort, large gaps remain in understanding how histone modifications coordinate pancreas development. SETD2, a predominant histone methyltransferase of H3K36me3, plays a key role in embryonic stem cell differentiation, whose role in organogenesis remains elusive. Here, by combination of cleavage under targets and tagmentation (CUT&Tag), assay for transposase-accessible chromatin using sequencing (ATAC-seq), and bulk RNA sequencing, we show a dramatic increase in the H3K36me3 level from the secondary transition phase and decipher the related transcriptional alteration. Using single-cell RNA sequencing, we define that pancreatic deletion of Setd2 results in abnormalities in both exocrine and endocrine lineages: hyperproliferative tip progenitor cells lead to abnormal differentiation; Ngn3

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Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

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Declaration of interests The authors declare no competing interests.