Genome-Wide Bovine H3K27me3 Modifications and the Regulatory Effects on Genes Expressions in Peripheral Blood Lymphocytes

Background Gene expression of lymphocytes was found to be influenced by histone methylation in mammals and trimethylation of lysine 27 on histone H3 (H3K27me3) normally represses genes expressions. Peripheral blood lymphocytes are the main source of somatic cells in the milk of dairy cows that vary frequently in response to the infection or injury of mammary gland and number of parities. Methods The genome-wide status of H3K27me3 modifications on blood lymphocytes in lactating Holsteins was performed via ChIP-Seq approach. Combined with digital gene expression (DGE) technique, the regulation effects of H3K27me3 on genes expressions were analyzed. Results The ChIP-seq results showed that the peaks of H3K27me3 in cows lymphocytes were mainly enriched in the regions of up20K (∼50%), down20K (∼30%) and intron (∼28%) of the genes. Only ∼3% peaks were enriched in exon regions. Moreover, the highest H3K27me3 modification levels were mainly around the 2 Kb upstream of transcriptional start sites (TSS) of the genes. Using conjoint analysis with DGE data, we found that H3K27me3 marks tended to repress target genes expressions throughout whole gene regions especially acting on the promoter region. A total of 53 differential expressed genes were detected in third parity cows compared to first parity, and the 25 down-regulated genes (PSEN2 etc.) were negatively correlated with H3K27me3 levels on up2Kb to up1Kb of the genes, while the up-regulated genes were not showed in this relationship. Conclusions The first blueprint of bovine H3K27me3 marks that mediates gene silencing was generated. H3K27me3 plays its repressed role mainly in the regulatory region in bovine lymphocytes. The up2Kb to up1Kb region of the down-regulated genes in third parity cows could be potential target of H3K27me3 regulation. Further studies are warranted to understand the regulation mechanisms of H3K27me3 on somatic cell count increases and milk losses in latter parities of cows.

[1]  Yuka Kanno,et al.  Global mapping of H3K4me3 and H3K27me3 reveals specificity and plasticity in lineage fate determination of differentiating CD4+ T cells. , 2009, Immunity.

[2]  R. Durbin,et al.  Mapping Quality Scores Mapping Short Dna Sequencing Reads and Calling Variants Using P

, 2022 .

[3]  A. Mortazavi,et al.  Genome-Wide Mapping of in Vivo Protein-DNA Interactions , 2007, Science.

[4]  J. Hultgren,et al.  Calving interval in dairy cows in relation to heifer rearing conditions in southwest Sweden. , 2010, Reproduction in domestic animals = Zuchthygiene.

[5]  N. Ragina,et al.  Polycomb gene expression and histone H3 lysine 27 trimethylation changes during bovine preimplantation development. , 2008, Reproduction.

[6]  Dustin E. Schones,et al.  Chromatin signatures in multipotent human hematopoietic stem cells indicate the fate of bivalent genes during differentiation. , 2009, Cell stem cell.

[7]  S. Berger,et al.  Histone modifications in transcriptional regulation. , 2002, Current opinion in genetics & development.

[8]  Jun Ni,et al.  Protein structural class prediction based on an improved statistical strategy , 2008, BMC Bioinformatics.

[9]  Ruiqiang Li,et al.  SOAP: short oligonucleotide alignment program , 2008, Bioinform..

[10]  Richard D. Kim,et al.  Reduced β-Amyloid Production and Increased Inflammatory Responses in Presenilin Conditional Knock-out Mice* , 2004, Journal of Biological Chemistry.

[11]  T. Lam,et al.  Characterization of distributions of somatic cell counts. , 2009, Journal of dairy science.

[12]  X. Liu,et al.  Genome-Wide and Organ-Specific Landscapes of Epigenetic Modifications and Their Relationships to mRNA and Small RNA Transcriptomes in Maize[W] , 2009, The Plant Cell Online.

[13]  Jeongseon Kim,et al.  Global DNA Hypomethylation in Peripheral Blood Leukocytes as a Biomarker for Cancer Risk: A Meta-Analysis , 2012, PloS one.

[14]  David A. Nix,et al.  Empirical methods for controlling false positives and estimating confidence in ChIP-Seq peaks , 2008, BMC Bioinformatics.

[15]  J. Herman,et al.  Promoter CpG island hypermethylation- and H3K9me3 and H3K27me3-mediated epigenetic silencing targets the deleted in colon cancer (DCC) gene in colorectal carcinogenesis without affecting neighboring genes on chromosomal region 18q21. , 2009, Carcinogenesis.

[16]  Yongli Yue,et al.  Multiple histone site epigenetic modifications in nuclear transfer and in vitro fertilized bovine embryos , 2010, Zygote.

[17]  Clifford A. Meyer,et al.  Model-based Analysis of ChIP-Seq (MACS) , 2008, Genome Biology.

[18]  J. Zeitlinger,et al.  Polycomb complexes repress developmental regulators in murine embryonic stem cells , 2006, Nature.

[19]  J. Hultgren,et al.  Heifer rearing conditions affect length of productive life in Swedish dairy cows. , 2009, Preventive veterinary medicine.

[20]  E. Greer,et al.  Transgenerational Epigenetic Inheritance of Longevity in C. elegans , 2011, Nature.

[21]  Richard D. Kim,et al.  Reduced beta-amyloid production and increased inflammatory responses in presenilin conditional knock-out mice. , 2004, The Journal of biological chemistry.

[22]  R. Vossen,et al.  Deep sequencing-based expression analysis shows major advances in robustness, resolution and inter-lab portability over five microarray platforms , 2008, Nucleic acids research.

[23]  N. Clode,et al.  The spatial organization of centromeric heterochromatin during normal human lymphopoiesis: evidence for ontogenically determined spatial patterns. , 2003, Experimental cell research.

[24]  K. Weigel,et al.  Assessment of the impact of somatic cell count on functional longevity in Holstein and Jersey cattle using survival analysis methodology. , 2005, Journal of dairy science.

[25]  Gordon B Mills,et al.  Loss of trimethylation at lysine 27 of histone H3 is a predictor of poor outcome in breast, ovarian, and pancreatic cancers , 2008, Molecular carcinogenesis.

[26]  Shiyi Chen,et al.  [Study on the relationships between polymorphisms of CXCR2 gene and milk quality and mastitis of dairy cow]. , 2008, Yi chuan = Hereditas.

[27]  Matthew D. Young,et al.  ChIP-seq analysis reveals distinct H3K27me3 profiles that correlate with transcriptional activity , 2011, Nucleic acids research.

[28]  M. Pfaffl,et al.  A new mathematical model for relative quantification in real-time RT-PCR. , 2001, Nucleic acids research.

[29]  H. Norman,et al.  Survival rates and productive herd life of dairy cattle in the United States. , 2006, Journal of dairy science.

[30]  Christoph D. Schmid,et al.  Rapid innovation in ChIP-seq peak-calling algorithms is outdistancing benchmarking efforts , 2011, Briefings Bioinform..

[31]  T. Kouzarides.  Chromatin Modifications and Their Function , 2007, Cell.

[32]  J. Hultgren,et al.  Lifetime risk and cost of clinical mastitis in dairy cows in relation to heifer rearing conditions in southwest Sweden. , 2009, Journal of dairy science.

[33]  Martin Kircher,et al.  High‐throughput DNA sequencing – concepts and limitations , 2010, BioEssays : news and reviews in molecular, cellular and developmental biology.

[34]  F. Quimby,et al.  Longitudinal evaluation of CD4+ and CD8+ peripheral blood and mammary gland lymphocytes in cows experimentally inoculated with Staphylococcus aureus. , 2000, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[35]  D. Kioussis,et al.  Epigenetic Flexibility Underlying Lineage Choices in the Adaptive Immune System , 2007, Science.

[36]  D. Boichard,et al.  Relationship between milk somatic-cell counts in the first lactation and clinical mastitis occurrence in the second lactation of French Holstein cows. , 2000, Preventive veterinary medicine.

[37]  Matteo Pellegrini,et al.  Promoter CpG methylation contributes to ES cell gene regulation in parallel with Oct4/Nanog, PcG complex, and histone H3 K4/K27 trimethylation. , 2008, Cell stem cell.

[38]  Suresh Cuddapah,et al.  The genomic landscape of histone modifications in human T cells , 2006, Proceedings of the National Academy of Sciences.

[39]  C. Audouard,et al.  Nuclear profiles of H3 histones trimethylated on Lys27 in bovine (Bos taurus) embryos obtained after in vitro fertilization or somatic cell nuclear transfer. , 2010, The Journal of reproduction and development.

[40]  A. Sharov,et al.  Age-associated alteration of gene expression patterns in mouse oocytes. , 2004, Human molecular genetics.

[41]  G. Pan,et al.  Whole-genome analysis of histone H3 lysine 4 and lysine 27 methylation in human embryonic stem cells. , 2007, Cell stem cell.

[42]  A. Koç.  A Study of Somatic Cell Counts in the Milk of Holstein-Friesian Cows Managed in Mediterranean Climatic Conditions , 2008 .

[43]  K. Pierce,et al.  Effects of breed, feeding system, and parity on udder health and milking characteristics. , 2007, Journal of dairy science.

[44]  Ryan D. Morin,et al.  Next-generation tag sequencing for cancer gene expression profiling. , 2009, Genome research.

[45]  S. Im,et al.  Epigenetic Regulation of Cytokine Gene Expression in T Lymphocytes , 2009, Yonsei medical journal.

[46]  Lai Wei,et al.  Regulation of microRNA expression and abundance during lymphopoiesis. , 2010, Immunity.

[47]  É. Vivier,et al.  Regulatory natural killer cells: new players in the IL-10 anti-inflammatory response. , 2009, Cell host & microbe.

[48]  Raymond K. Auerbach,et al.  Efficient yeast ChIP-Seq using multiplex short-read DNA sequencing , 2009 .

[49]  R. Cue,et al.  Milk losses associated with somatic cell counts per breed, parity and stage of lactation in Canadian dairy cattle , 2008 .

[50]  K. Petrovski,et al.  Effect of parity on lymphocytes in peripheral blood and colostrum of healthy Holstein dairy cows. , 2010, Canadian journal of veterinary research = Revue canadienne de recherche veterinaire.

[51]  J. A. Arias,et al.  Epigenetic Regulation of Milk Production in Dairy Cows , 2010, Journal of Mammary Gland Biology and Neoplasia.

[52]  Juri Rappsilber,et al.  A model for transmission of the H3K27me3 epigenetic mark , 2008, Nature Cell Biology.

[53]  Dustin E. Schones,et al.  High-Resolution Profiling of Histone Methylations in the Human Genome , 2007, Cell.