Single Nucleus Methylation Sequencing of Mouse Pituitary
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 regulons whose composition and function within specific cell types were shaped by the promoter accessibility state of target genes. Co-accessibility analysis comprehensively identified putative cis-regulatory regions, including a domain 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 [link] is a public resource for elucidating cell-type specific gene regulatory mechanisms and principles of transcription circuit control. This GEO series contain raw (FASTQ) and processed data (ALLC) files for the sn methylation dataset generated by the snmC-seq2 method. Overall design: Apply snmC-seq2 to individual nuclei isolated from pituitary pooled from 30 adult male C57BL/6 mice