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A comprehensive characterization of regulatory elements in the chicken genome across tissues will have substantial impacts on both fundamental and applied research. Here, we systematically identified and characterized regulatory elements in the chicken genome by integrating 377 genome-wide sequencing datasets from 23 adult tissues. In total, we annotated 1.57 million regulatory elements, representing 15 distinct chromatin states, and predicted about 1.2 million enhancer-gene pairs and 7662 super-enhancers. This functional annotation of the chicken genome should have wide utility on identifying regulatory elements accounting for gene regulation underlying domestication, selection, and complex trait regulation, which we explored. In short, this comprehensive atlas of regulatory elements provides the scientific community with a valuable resource for chicken genetics and genomics.

The functional annotation of livestock genomes is crucial for understanding the molecular mechanisms that underpin complex traits of economic importance, adaptive evolution and comparative genomics. Here, we provide the most comprehensive catalogue to date of regulatory elements in the pig (Sus scrofa) by integrating 223 epigenomic and transcriptomic data sets, representing 14 biologically important tissues. We systematically describe the dynamic epigenetic landscape across tissues by functionally annotating 15 different chromatin states and defining their tissue-specific regulatory activities. We demonstrate that genomic variants associated with complex traits and adaptive evolution in pig are significantly enriched in active promoters and enhancers. Furthermore, we reveal distinct tissue-specific regulatory selection between Asian and European pig domestication processes. Compared with human and mouse epigenomes, we show that porcine regulatory elements are more conserved in DNA sequence, under both rapid and slow evolution, than those under neutral evolution across pig, mouse, and human. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating 47 human genome-wide association studies, we demonstrate that, depending on the traits, mouse or pig might be more appropriate biomedical models for different complex traits and diseases.

Preimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours. Cultures were subsequently assessed for epithelial morphometry, bioelectrical properties, and gene expression responses (steroid hormone signaling, oviductal function, immune response, and apoptosis). Results confirmed the suppressive role of P4 in regulating oviduct epithelium characteristics, which was partially opposed by E2. Besides increasing the ratio of ciliated cells, cortisol antagonized the effect of P4 on epithelial polarity and modified sex steroid–induced changes in transepithelial electrical properties. Both sex steroids affected the glucocorticoid receptor expression, while cortisol downregulated the expression of progesterone receptor. The overall gene expression pattern suggests that sex steroid dominates the cotreatment, but cortisol contributes by altering the gene responses to sex steroids. We conclude that besides its individual action, maternal cortisol interplays with sex steroids at phenotypic and molecular levels in the oviduct epithelium, thereby influencing the microenvironment of gametes and early embryos. [ABSTRACT FROM AUTHOR]

Abstract Background Avian influenza virus (AIV) outbreaks are worldwide threats to both poultry and humans. Our previous study suggested microRNAs (miRNAs) play significant roles in the regulation of host response to AIV infection in layer chickens. The objective of this study was to test the hypothesis if genetic background play essential role in the miRNA regulation of AIV infection in chickens and if miRNAs that were differentially expressed in layer with AIV infection would be modulated the same way in broiler chickens. Furthermore, by integrating with parallel mRNA expression profiling, potential molecular mechanisms of host response to AIV infection can be further exploited. Results Total RNA isolated from the lungs of non-infected and low pathogenic H5N3 infected broilers at four days post-infection were used for both miRNA deep sequencing and mRNA microarray analyses. A total of 2.6 M and 3.3 M filtered high quality reads were obtained from infected and non-infected chickens by Solexa GA-I Sequencer, respectively. A total of 271 miRNAs in miRBase 16.0 were identified and one potential novel miRNA was discovered. There were 121 miRNAs differentially expressed at the 5% false discovery rate by Fisher’s exact test. More miRNAs were highly expressed in infected lungs (108) than in non-infected lungs (13), which was opposite to the findings in layer chickens. This result suggested that a different regulatory mechanism of host response to AIV infection mediated by miRNAs might exist in broiler chickens. Analysis using the chicken 44 K Agilent microarray indicated that 508 mRNAs (347 down-regulated) were differentially expressed following AIV infection. Conclusions A comprehensive analysis combining both miRNA and targeted mRNA gene expression suggests that gga-miR-34a, 122–1, 122–2, 146a, 155, 206, 1719, 1594, 1599 and 451, and MX1, IL-8, IRF-7, TNFRS19 are strong candidate miRNAs or genes involved in regulating the host response to AIV infection in the lungs of broiler chickens. Further miRNA or gene specific knock-down assay is warranted to elucidate underlying mechanism of AIV infection regulation in the chicken.

Preimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours. Cultures were subsequently assessed for epithelial morphometry, bioelectrical properties, and gene expression responses (steroid hormone signaling, oviductal function, immune response, and apoptosis). Results confirmed the suppressive role of P4 in regulating oviduct epithelium characteristics, which was partially opposed by E2. Besides increasing the ratio of ciliated cells, cortisol antagonized the effect of P4 on epithelial polarity and modified sex steroid–induced changes in transepithelial electrical properties. Both sex steroids affected the glucocorticoid receptor expression, while cortisol downregulated the expression of progesterone receptor. The overall gene expression pattern suggests that sex steroid dominates the cotreatment, but cortisol contributes by altering the gene responses to sex steroids. We conclude that besides its individual action, maternal cortisol interplays with sex steroids at phenotypic and molecular levels in the oviduct epithelium, thereby influencing the microenvironment of gametes and early embryos. [ABSTRACT FROM AUTHOR]

To investigate the effects of dietary iron (Fe) and age on Fe metabolism, we used 36 weaned barrows in a 2 x 3 design with 2 concentrations of dietary Fe [97 (control) and 797 (high Fe) mg Fe/kg dry matter] and 3 time points of tissue collection (after 21,42, or 63 d on diets). Pigs were weighed and bled on d 0, 20, 41, and 62. High Fe reduced feed efficiency but did not affect pig weight gain. Blood hemoglobin concentrations and Fe concentrations of liver, intestine, and heart were increased by high dietary Fe on all days. Concentrations of liver and heart Fe increased with age. As determined by quantitative real- time PCR, hepatic expression of hepcidin (HAMP) in pigs given the high-Fe diet was 6.25-fold that of control pigs. In the intestine, relative mRNA levels of ferroportin, divalent metal transporter 1, and transferrin receptor were downregulated by high Fe. Expression of an alternative route of Fe absorption, solute carrier family 39 member 14 (SLC39A14), was downregulated in the intestine of pigs fed high dietary Fe. Additionally, duodenal mRNA level of certain genes including scavenger receptor class A, member 5, and frataxin decreased with age of the animal. Our findings indicate new roles in Fe metabolism for several mineral metabolism-associated genes and that some of these genes, such as SLC39A14, may be regulated in response to dietary Fe in pigs. Additionally, the expression of some genes examined in this study was affected by age, suggesting age dependency of Fe metabolism in pigs. J. Nutr. 140: 271-277, 2010. doi: 10.3945/jn.109.112722.

To investigate the effects of dietary iron (Fe) on manganese (Mn) metabolism, 24 weaned pigs (21 d old) were blocked by litter and weight and randomly assigned to the following treatments: 1) no supplemental Fe [low Fe (L-Fe)]; 2) 100 mg supplemental Fe/kg (adequate Fe (A-Fe)]; and 3) 500 mg supplemental Fe/kg [high Fe (H-Fe)]. The basal diet was analyzed to contain 20 mg Fe/kg. Tissues were harvested after 32 d of feeding. Daily gain (least square means + SEM) was greater in A-Fe pigs (328.3 [+ or -] 29.9 g/d) than in L-Fe pigs (224.0 [+ or -] 11.2 g/d). Hemoglobin concentrations on d 32 were lower in L-Fe pigs (62 [+ or -] 3.5 g/L) than in A-Fe pigs (128 [+ or -] 5.6 g/L) and did not differ between pigs fed A-Fe and H-Fe (133 [+ or -] 12.0 g/L). Liver Fe increased with increasing dietary Fe. Relative hepatic hepcidin expression was greater in pigs fed A-Fe and H-Fe than in those fed L-Fe. Relative expressions of duodenal divalent metal transporter 1 (DMT1) and solute carrier family 39 member 14 (ZIP14) were increased in L-Fe pigs compared with H-Fe pigs. Liver copper (Cu) was higher in L-Fe (0.56 [+ or -] 0.04 mmol/kg) and H-Fe (0.58 [+ or -] 0.04 mmol/kg) pigs than in A-Fe pigs (0.40 [+ or -] 0.04 mmol/kg). Liver Mn was lower in H-Fe pigs (0.15 [+ or -] 0.01 mmol/kg) than in A-Fe (0.23 [+ or -] 0.02 mmol/kg) or L-Fe pigs (0.20 [+ or -] 0.02 mmol/kg). Duodenal Mn concentrations were greater in L-Fe pigs than in A-Fe or H-Fe pigs. Fe deficiency in pigs increased gene expression of duodenal metal transporters (DMT1 and ZIP14) and supplementation with H-Fe reduced expression of DMT1 and ZIP14, which may have decreased absorption of Mn. J. Nutr. 139: 1474-1479, 2009.