In Vivo Epigenomic Profiling of Germ Cells Reveals Germ Cell Molecular Signatures

• Published in: Developmental cell Vol. 24; no. 3; pp. 324 - 333
• Main Authors: Ng, Jia-Hui, Kumar, Vibhor, Muratani, Masafumi, Kraus, Petra, Yeo, Jia-Chi, Yaw, Lai-Ping, Xue, Kun, Lufkin, Thomas, Prabhakar, Shyam, Ng, Huck-Hui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 11.02.2013
• Subjects: Animals; Chromatin; Chromosome Mapping; Embryonic Stem Cells - enzymology; Embryonic Stem Cells - metabolism; Enhancer Elements, Genetic; Epigenesis, Genetic - genetics; Genomics; Germ Cells - enzymology; Germ Cells - metabolism; Histone-Lysine N-Methyltransferase - genetics; Histone-Lysine N-Methyltransferase - metabolism; Histones - genetics; Histones - metabolism; Mice; Promoter Regions, Genetic; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Retroelements
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2012.12.011

The limited number of in vivo germ cells poses an impediment to genome-wide studies. Here, we applied a small-scale chromatin immunoprecipitation sequencing (ChIP-seq) method on purified mouse fetal germ cells to generate genome-wide maps of four histone modifications (H3K4me3, H3K27me3, H3K27ac, and H2BK20ac). Comparison of active chromatin state between somatic, embryonic stem, and germ cells revealed promoters and enhancers needed for stem cell maintenance and germ cell development. We found the nuclear receptor Nr5a2 motif to be enriched at a subset of germ cell cis-regulatory regions, and our results implicate Nr5a2 in germ cell biology. Interestingly, in germ cells, the H3K27me3 histone modification occurs more frequently at regions that are enriched for retrotransposons and MHC genes, indicating that these loci are specifically silenced in germ cells. Together, our study provides genome-wide histone modification maps of in vivo germ cells and reveals the molecular chromatin signatures of germ cells. [Display omitted] ► Modified small-scale ChIP-seq method applicable to small number of cells ► Genome-wide maps of H3K4me3, H3K27me3, H3K27ac, and H2BK20ac of germ cells in vivo ► Identification of active and inactive regulatory elements in germ cells in vivo ► Germ cell H3K27me3 regions are enriched for retrotransposon repeats Ng et al. used a modified small-scale ChIP-seq method to generate genome-wide maps of H3K4me3, H3K27me3, H3K27ac, and H2BK20ac for in vivo fetal germ cells. These histone modification data sets enabled the identification of active and inactive chromatin regions, thereby uncovering key molecular signatures and developmental regulators of germ cells.