79 research outputs found
Leadership in African American Politics: The Role of President Obama on the Issue of Same-Sex Marriage
In 2008, African Americans overwhelmingly supported Senator Obama in his bid for the Presidency. Their supported averaged at 95% of African American voters. At the same time that Senator Obama was on the ballet, Prop 8 - legislation designed to amend California\u27s Constitution to define marriage as between a man and woman - was passed with a large majority of African American support. Why did strong Democrats vote in favor of a law that most Democrats rejected? Previous research has concluded it was the role of the Black Church in African American politics that moves the community to a more conservative ideology on social issues. Using polling data from 2010 and 2012, I will look at if President Obama had any impact on views on African Americans to see if he has sway in the same way as the Black Church. The key to these two data sets is that he changed his opinion on the issue of same-sex marriage very publically between these two polls. If he had an effect, a sizable change should show African American views on same-sex marriage
Evolution of YY1, YY2, REX1 and DNA-binding motifs in vertebrate genomes
Transcription factors are important for many aspects of gene regulation in eukaryotes. YY1 (Yin-Yang 1) is a particularly interesting example of a highly conserved zinc-finger transcription factor, involved in transcriptional activation, repression, initiation, and in chromatin modification. YY1 is ubiquitously expressed in mammals, and its binding sites are found in ~10% of human genes as well as in repetitive elements. It is a targeting protein of the Polycomb complex and is involved in mammalian genomic imprinting. First, we explored the evolutionary history of YY1 using 62 species and formation of its paralogs, YY2 and REX1, which are found in mammals, and Pho and Phol, which are found in Drosophila. We confirmed the specificity of the consensus YY1 binding site and the differences of the target binding motifs of YY2 and REX1 which are reflected in their amino acid sequences. We found that the core motif, CCAT, is conserved for all three homologs and that YY2 and REX1 were produced via retrotransposition events early in the mammalian lineage. Second, we identified unusual clusters of YY1-binding motifs found in the coding regions of olfactory receptor genes (OLFRs) in mammals but not in fish. Olfactory genes provide scent detection and are the largest class of genes in mammals. Statistical analysis indicates that the core of the YY1-binding motifs cannot be acounted for by conserved amino acid motifs or overall protein homology. Thus selection has acted at the DNA level rather than at the protein level in preserving these YY1-binding sites within coding regions. Therefore, YY1 is likely to play a crucial role in regulating the expression of OLFRs. Third, we produced a new method of microarray data analysis predicated on the positions of genes along a chromosome as well as their expression levels. This technique is supplementary to traditional microarray data analysis and adds a new dimension to finding target genes of interest by looking for co-regulation. Overall, this work provides a coherent background to the evolution of YY1 and its homologs. It provides strong evidence that coding sequences of genes can encode information both at the DNA level and the protein level
YY1's DNA-Binding motifs in mammalian olfactory receptor genes
<p>Abstract</p> <p>Background</p> <p>YY1 is an epigenetic regulator for a large number of mammalian genes. While performing genome-wide YY1 binding motif searches, we discovered that the olfactory receptor (OLFR) genes have an unusual cluster of YY1 binding sites within their coding regions. The statistical significance of this observation was further analyzed.</p> <p>Results</p> <p>About 45% of the olfactory genes in the mouse have a range of 4-8 YY1 binding sites within their respective 1 kb coding regions. Statistical analyses indicate that this enrichment of YY1 motifs has likely been driven by unknown selection pressures at the DNA level, but not serendipitously by some peptides enriched within the OLFR genes. Similar patterns are also detected in the OLFR genes of all mammals analyzed, but not in the OLFR genes of the fish lineage, suggesting a mammal-specific phenomenon.</p> <p>Conclusion</p> <p>YY1, or YY1-related transcription factors, may help regulate olfactory receptor genes. Furthermore, the protein-coding regions of vertebrate genes can contain <it>cis</it>-regulatory elements for transcription factor binding as well as codons.</p
Retroposition and evolution of the DNA-binding motifs of YY1, YY2 and REX1
YY1 is a DNA-binding transcription factor found in both vertebrates and invertebrates. Database searches identified 62 YY1 related sequences from all the available genome sequences ranging from flying insects to human. These sequences are characterized by high levels of sequence conservation, ranging from 66% to 100% similarity, in the zinc finger DNA-binding domain of the predicted proteins. Phylogenetic analyses uncovered duplication events of YY1 in several different lineages, including flies, fish and mammals. Retroposition is responsible for generating one duplicate in flies, PHOL from PHO, and two duplicates in placental mammals, YY2 and Reduced Expression 1 (REX1) from YY1. DNA-binding motif studies have demonstrated that YY2 still binds to the same consensus sequence as YY1 but with much lower affinity. In contrast, REX1 binds to DNA motifs divergent from YY1, but the binding motifs of REX1 and YY1 share some similarity at their core regions (5′-CCAT-3′). This suggests that the two duplicates, YY2 and REX1, although generated through similar retroposition events have undergone different selection schemes to adapt to new roles in placental mammals. Overall, the conservation of YY2 and REX1 in all placental mammals predicts that each duplicate has co-evolved with some unique features of eutherian mammals
Phylogenetic and DNA methylation analysis reveal novel regions of variable methylation in the mouse IAP class of transposons
Abstract
Background
Select retrotransposons in the long terminal repeat (LTR) class exhibit interindividual variation in DNA methylation that is altered by developmental environmental exposures. Yet, neither the full extent of variability at these “metastable epialleles,” nor the phylogenetic relationship underlying variable elements is well understood. The murine metastable epialleles, Avy and CabpIAP, result from independent insertions of an intracisternal A particle (IAP) mobile element, and exhibit remarkably similar sequence identity (98.5%).
Results
Utilizing the C57BL/6 genome we identified 10802 IAP LTRs overall and a subset of 1388 in a family that includes Avy and CabpIAP. Phylogenetic analysis revealed two duplication and divergence events subdividing this family into three clades. To characterize interindividual variation across clades, liver DNA from 17 isogenic mice was subjected to combined bisulfite and restriction analysis (CoBRA) for 21 separate LTR transposons (7 per clade). The lowest and highest mean methylation values were 59% and 88% respectively, while methylation levels at individual LTRs varied widely, ranging from 9% to 34%. The clade with the most conserved elements had significantly higher mean methylation across LTRs than either of the two diverged clades (p = 0.040 and p = 0.017). Within each mouse, average methylation across all LTRs was not significantly different (71%-74%, p > 0.99).
Conclusions
Combined phylogenetic and DNA methylation analysis allows for the identification of novel regions of variable methylation. This approach increases the number of known metastable epialleles in the mouse, which can serve as biomarkers for environmental modifications to the epigenome.http://deepblue.lib.umich.edu/bitstream/2027.42/112312/1/12864_2012_Article_4665.pd
The role of environmental exposures and the epigenome in health and disease
Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152782/1/em22311_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152782/2/em22311.pd
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Perinatal Lead (Pb) Exposure Results in Sex-Specific Effects on Food Intake, Fat, Weight, and Insulin Response across the Murine Life-Course
Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age
Epigenome‐wide DNA methylation analysis implicates neuronal and inflammatory signaling pathways in adult murine hepatic tumorigenesis following perinatal exposure to bisphenol A
Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/133545/1/em22024.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/133545/2/em22024_am.pd
Changes in Gene Expression Foreshadow Diet-Induced Obesity in Genetically Identical Mice
High phenotypic variation in diet-induced obesity in male C57BL/6J inbred mice suggests a molecular model to investigate non-genetic mechanisms of obesity. Feeding mice a high-fat diet beginning at 8 wk of age resulted in a 4-fold difference in adiposity. The phenotypes of mice characteristic of high or low gainers were evident by 6 wk of age, when mice were still on a low-fat diet; they were amplified after being switched to the high-fat diet and persisted even after the obesogenic protocol was interrupted with a calorically restricted, low-fat chow diet. Accordingly, susceptibility to diet-induced obesity in genetically identical mice is a stable phenotype that can be detected in mice shortly after weaning. Chronologically, differences in adiposity preceded those of feeding efficiency and food intake, suggesting that observed difference in leptin secretion is a factor in determining phenotypes related to food intake. Gene expression analyses of adipose tissue and hypothalamus from mice with low and high weight gain, by microarray and qRT-PCR, showed major changes in the expression of genes of Wnt signaling and tissue re-modeling in adipose tissue. In particular, elevated expression of SFRP5, an inhibitor of Wnt signaling, the imprinted gene MEST and BMP3 may be causally linked to fat mass expansion, since differences in gene expression observed in biopsies of epididymal fat at 7 wk of age (before the high-fat diet) correlated with adiposity after 8 wk on a high-fat diet. We propose that C57BL/6J mice have the phenotypic characteristics suitable for a model to investigate epigenetic mechanisms within adipose tissue that underlie diet-induced obesity
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