@article{4124, keywords = {Animals, Promoter Regions, Genetic, Regulon, Gene Expression Regulation, Mice, Inbred C57BL, Models, Genetic, Female, Male, Transcriptome, Chromatin, Gene Regulatory Networks, DNA Methylation, Sex Factors, Pituitary Gland}, author = {Frederique Ruf-Zamojski and Zidong Zhang and Michel Zamojski and Gregory Smith and Natalia Mendelev and Hanqing Liu and German Nudelman and Mika Moriwaki and Hanna Pincas and Rosa Castanon and Venugopalan Nair and Nitish Seenarine and Mary Amper and Xiang Zhou and Luisina Ongaro and Chirine Toufaily and Gauthier Schang and Joseph Nery and Anna Bartlett and Andrew Aldridge and Nimisha Jain and Gwen Childs and Olga Troyanskaya and Joseph Ecker and Judith Turgeon and Corrine Welt and Daniel Bernard and Stuart Sealfon}, title = {Single nucleus multi-omics regulatory landscape of the murine pituitary.}, abstract = {

To provide a multi-omics resource and investigate transcriptional regulatory mechanisms, we profile the transcriptome, chromatin accessibility, and methylation status of over 70,000 single nuclei (sn) from adult~mouse pituitaries. Paired snRNAseq and snATACseq datasets from individual animals highlight a continuum between developmental epigenetically-encoded cell types and transcriptionally-determined transient cell states. Co-accessibility analysis-based identification of a putative Fshb cis-regulatory domain that overlaps the fertility-linked rs11031006 human polymorphism, followed by experimental validation illustrate the use of this resource for hypothesis generation. We also identify transcriptional and chromatin accessibility programs distinguishing each major cell type. Regulons, which are co-regulated gene sets sharing binding sites for a common transcription factor driver, recapitulate cell type clustering. We identify both cell type-specific and sex-specific regulons that are highly correlated with promoter accessibility, but not with methylation state, supporting the centrality of chromatin accessibility in shaping cell-defining transcriptional programs. The sn multi-omics atlas is accessible at snpituitaryatlas.princeton.edu.

}, year = {2021}, journal = {Nat Commun}, volume = {12}, pages = {2677}, month = {2021 May 11}, issn = {2041-1723}, doi = {10.1038/s41467-021-22859-w}, language = {eng}, }