Genome-wide analysis of differential transcriptional and epigenetic variability across human immune cell types

Abstract Background A healthy immune system requires immune cells that adapt rapidly to environmental challenges. This phenotypic plasticity can be mediated by transcriptional and epigenetic variability. Results We apply a novel analytical approach to measure and compare transcriptional and epigenetic variability genome-wide across CD14+CD16− monocytes, CD66b+CD16+ neutrophils, and CD4+CD45RA+ naïve T cells from the same 125 healthy individuals. We discover substantially increased variability in neutrophils compared to monocytes and T cells. In neutrophils, genes with hypervariable expression are found to be implicated in key immune pathways and are associated with cellular properties and environmental exposure. We also observe increased sex-specific gene expression differences in neutrophils. Neutrophil-specific DNA methylation hypervariable sites are enriched at dynamic chromatin regions and active enhancers. Conclusions Our data highlight the importance of transcriptional and epigenetic variability for the key role of neutrophils as the first responders to inflammatory stimuli. We provide a resource to enable further functional studies into the plasticity of immune cells, which can be accessed from: http://blueprint-dev.bioinfo.cnio.es/WP10/hypervariability

Isolation And Characterization Of Y Chromosome Dna Probes

A sorted, cloned Y chromosome phage library was screened for unique Y chromosome sequences. Of the thousands of plaques screened, 13 did not hybridize to radiolabeled 46, XX total chromosomal DNA. Three plaques were characterized further. Clone Y1 hybridized to multiple restriction enzyme fragments in both male and female DNA with more intense bands in male DNA. Clone Y2, also found in female and male DNA, is probably located in the pseudosutosomal region because extra copies of either the X or Y chromosomes increased Y2 restriction enzyme fragment intensity in total cellular DNA. Clone Y5 was male specific in three of four restriction enzyme digests althouth in the fourth a light hybridizing band was observed in both male and female DNA. Clone Y5 was sublocalized to band Yq 11.22 by hybridization to a panel of cellular DNA from patients with Y chromosome rearrangements. Clone Y5 can be used to test for retention of the proximally long arm Y suggested to cause gonadal cancer in carrier females. The long series of GA repeats in Y5, anticipated to be polymorphic, may provide a sensitive means to follow Y chromosome variation in human populations. © 1992.1891581589Schonberg, (1989) Handbook of Human Growth and Developmental Biology, 2, pp. 229-237. , 2nd Edition, E. Meisami, P. Timivas, CRC Press, Boca Raton, FLPage, de la Chapelle, Weissenbach, (1985) Nature, 315, pp. 224-226Disteche, Casanova, Saal, Friedman, Sybert, Graham, Thuline, Page, (1986) PNAS, 83, pp. 7841-7844Vergnaud, Page, Simmler, Brown, Rouyer, Noel, Botstein, Weissenbach, (1986) Am. J. Hum. Genet, 38, pp. 109-124McLaren, Simpson, Tomonari, Chandler, Hogg, (1984) Nature, 312, pp. 552-555Simpson, Chandler, Goulmy, Disteche, Ferguson-Smith, Page, (1987) Nature, 326, pp. 876-878Koopman, Gubbay, Vivian, Goodfellow, Lovell-Badge, (1991) Nature, 351, pp. 117-121Washburn, Eicher, (1983) Nature, 303, pp. 338-34015Rouyer, Simmler, Johnsson, Vergnaud, Cooke, Weissenbach, (1986) Nature, 319, pp. 291-295Yen, Marsh, Allen, Taai, Ellison, Connolly, Neiswanger, Shapiro, (1988) Cell, 55, pp. 1123-1138de la Chapelle, The etiology of maleness in XX men (1981) Human Genetics, 58, pp. 105-116Page, Mosher, Simpson, Fisher, Mardon, Pollack, McGillivray, Brown, The sex-determining region of the human Y chromosome encodes a finger protein (1987) Cell, 51, pp. 1091-1104Lau, (1984) The Y Chromosome, Part A: Basic Characteristics of the Y Chromosome, pp. 177-192. , A. Sandberg, Alan R. Liss, New YorkNgo, Vergnaud, Johnsson, Lucotte, Weissenbach, (1986) Am. J. Hum. Genet, 38, pp. 407-418Wolman, David, Koo, (1985) The Y chromosome. Part A: basic characteristics of the Y chromosome, pp. 477-505. , A. Sandberg, Alan R. Liss, NYGemmill, Pearce-Birge, Bixenman, Hecht, Allanson, (1987) Am. J. Hum. Genet, 41, pp. 157-167Goosens, Kan, [49] DNA analysis in the diagnosis of hemoglobin disorders (1981) Method. Enzymol, 76, pp. 805-817Van Dilla, Deaven, Construction of gene libraries for each human chromosome (1990) Cytometry, 11, pp. 208-218Sambrook, Fritsch, Maniatis, (1989) Molecular Cloning: a Laboratory Manual, , 2nd Edition, Cold Spring Harbor Press, NYRigby, Dieckmann, Rhodes, Berg, (1977) J. Mol. Biol, 113, pp. 237-251Feinberg, Vogelstein, (1984) Anal. Biochem, 137, pp. 266-267Farah, Garmes, Cavalcanti, Mello, Porelli, Ramos, Sartorato, (1991) Brazilian J. Med. Biol. Res, 24, pp. 149-156Southern, (1975) J. Mol. Biol, 98, pp. 503-51