title: In situ histone landscape of nephrogenesis.
abstract: In the developing kidney, self-renewing progenitors respond to inductive signaling from the adjacent branching ureteric bud by undergoing mesenchyme-to-epithelium transition. Nascent nephrons subsequently undergo elongation, segmentation, and differentiation into a mature renal epithelium with diverse functions. Epigenetic mechanisms have been implicated in impacting cell fate decisions during nephrogenesis; however, the chromatin landscape of nephron progenitors and daughter differentiating cells are largely unknown. Here, we examined the spatiotemporal expression patterns of histone H3 methylation and histone methyltransferases in E15.5 mouse kidneys. Kidney sections were probed with antibodies against histone modifications, enzymes, and markers of progenitors and differentiation. The results revealed that: (1) nephron progenitor cells exhibit a broad histone methylation signature that comprises both "active" and "repressive" marks (H3K4me3/K9me3/K27me3/R2me2/R17me2); (2) nascent nephrons retain high H3K4me3 but show downregulation of H3K9/K27me3 and; (3) maturing epithelial tubules acquire high levels of H3K79me2/3. Consistent with respective histone marks, the H3K4 methyltransferase, Ash2l, is expressed in progenitors and nascent nephrons, whereas the H3K9/K27 methyltransferases, G9a/Ezh2, are more enriched in progenitors than nascent nephrons. We conclude that combinatorial histone signatures correlate with cell fate decisions during nephrogenesis.
authors.affiliation: Department of Pediatrics; Tulane University School of Medicine; New Orleans, LA USA; Biomedical Sciences Program; Tulane University School of Medicine; New Orleans, LA USA.
authors.forename: Nathan
authors.initials: N
authors.lastname: McLaughlin
authors.affiliation: Department of Pediatrics; Tulane University School of Medicine; New Orleans, LA USA; Biomedical Sciences Program; Tulane University School of Medicine; New Orleans, LA USA.
authors.forename: Fenglin
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Pediatrics; Tulane University School of Medicine; New Orleans, LA USA; The Renal and Hypertension Center of Excellence; Tulane University School of Medicine; New Orleans, LA USA.
authors.forename: Zubaida
authors.initials: Z
authors.lastname: Saifudeen
authors.affiliation: Department of Pediatrics; Tulane University School of Medicine; New Orleans, LA USA; The Renal and Hypertension Center of Excellence; Tulane University School of Medicine; New Orleans, LA USA.
authors.forename: Samir S
authors.initials: SS
authors.lastname: El-Dahr
mesh_terms: D000818:Animals; D001120:Arginine / Q000378:metabolism; D002454:Cell Differentiation; D002843:Chromatin / Q000378:metabolism; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D007668:Kidney / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D051379:Mice; D009399:Nephrons / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D038081:Organogenesis; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones; D001120:Arginine; D000076983:Histone Methyltransferases; D011495:Histone-Lysine N-Methyltransferase; D008239:Lysine
keywords: chromatin landscape; differentiation; histone methylation; histone modifications; kidney development; nephrogenesis; nephron progenitors