RT Journal Article SR Electronic T1 Single nucleus multi-omics regulatory atlas of the murine pituitary JF bioRxiv FD Cold Spring Harbor Laboratory SP 2020.06.06.138024 DO 10.1101/2020.06.06.138024 A1 Frederique Ruf-Zamojski A1 Zidong Zhang A1 Michel Zamojski A1 Gregory R. Smith A1 Natalia Mendelev A1 Hanqing Liu A1 German Nudelman A1 Mika Moriwaki A1 Hanna Pincas A1 Rosa Gomez Castanon A1 Venugopalan D. Nair A1 Nitish Seenarine A1 Mary Anne S. Amper A1 Xiang Zhou A1 Luisina Ongaro A1 Chirine Toufaily A1 Gauthier Schang A1 Joseph R. Nery A1 Anna Bartlett A1 Andrew Aldridge A1 Nimisha Jain A1 Gwen V. Childs A1 Olga G. Troyanskaya A1 Joseph R. Ecker A1 Judith L. Turgeon A1 Corrine K. Welt A1 Daniel J. Bernard A1 Stuart C. Sealfon YR 2020 UL http://biorxiv.org/content/early/2020/06/11/2020.06.06.138024.abstract AB The pituitary regulates growth, reproduction and other endocrine systems. To investigate transcriptional network epigenetic mechanisms, we generated paired single nucleus (sn) transcriptome and chromatin accessibility profiles in single mouse pituitaries and genome-wide sn methylation datasets. Our analysis provided insight into cell type epigenetics, regulatory circuit and gene control mechanisms. Latent variable pathway analysis detected corresponding transcriptome and chromatin accessibility programs showing both inter-sexual and inter-individual variation. Multi-omics analysis of gene regulatory networks identified cell type-specific regulons whose composition and function were shaped by the promoter accessibility state of target genes. Co-accessibility analysis comprehensively identified putative cis-regulatory regions, including a domain 17kb upstream of Fshb that overlapped the fertility-linked rs11031006 human polymorphism. In vitro CRISPR-deletion at this locus increased Fshb levels, supporting this domain’s inferred regulatory role. The sn pituitary multi-omics atlas (snpituitaryatlas.princeton.edu) is a public resource for elucidating cell type-specific gene regulatory mechanisms and principles of transcription circuit control.Competing Interest StatementThe authors have declared no competing interest.