| 1. |
|
|
| 2. |
- Birney, Ewan, et al.
(author)
-
Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot project
- 2007
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 447:7146, s. 799-816
-
Journal article (peer-reviewed)abstract
- We report the generation and analysis of functional data from multiple, diverse experiments performed on a targeted 1% of the human genome as part of the pilot phase of the ENCODE Project. These data have been further integrated and augmented by a number of evolutionary and computational analyses. Together, our results advance the collective knowledge about human genome function in several major areas. First, our studies provide convincing evidence that the genome is pervasively transcribed, such that the majority of its bases can be found in primary transcripts, including non-protein-coding transcripts, and those that extensively overlap one another. Second, systematic examination of transcriptional regulation has yielded new understanding about transcription start sites, including their relationship to specific regulatory sequences and features of chromatin accessibility and histone modification. Third, a more sophisticated view of chromatin structure has emerged, including its inter-relationship with DNA replication and transcriptional regulation. Finally, integration of these new sources of information, in particular with respect to mammalian evolution based on inter- and intra-species sequence comparisons, has yielded new mechanistic and evolutionary insights concerning the functional landscape of the human genome. Together, these studies are defining a path for pursuit of a more comprehensive characterization of human genome function.
|
|
| 3. |
- Rada-Iglesias, A., et al.
(author)
-
Histone H3 lysine 27 trimethylation in adult differentiated colon associated to cancer DNA hypermethylation
- 2009
-
In: Epigenetics. - 1559-2294. ; 4:2, s. 107-13
-
Journal article (peer-reviewed)abstract
- DNA hypermethylation of gene promoters is a common epigenetic alteration occurring in cancer cells. However, little is known about the mechanisms instructing these cancer-specific DNA hypermethylation events. Recent reports have suggested that genes bound by polycomb/Histone H3 lysine 27 trimethylation (H3K27me3) in embryonic stem (ES) cells are frequent targets for cancer-specific DNA hypermethylation. This polycomb-premarking is assumed to be restrained to ES cells, even though almost no polycomb/H3K27me3 binding profiles are available for differentiated tissues. We generated H3K27me3 profiles in human normal colon and they significantly overlapped with those of ES cells and genes hypermethylated in colorectal cancer (CRC). Moreover, colon H3K27me3 was more restricted to genes hypermethylated in CRC, while ES H3K27me3 was also common in genes hypermethylated in other tumors. Therefore, the suggested polycomb pre-marking of genes for cancer DNA hypermethylation is not necessarily limited to ES or early precursor cells but can occur later in differentiated tissues.
|
|
| 4. |
|
|
| 5. |
- Bergström, Ulrika, et al.
(author)
-
Differential gene expression in the olfactory bulb following exposure to the olfactory toxicant 2,6-dichlorophenyl methylsulphone and its 2,5-dichlorinated isomer in mice
- 2007
-
In: Neurotoxicology. - : Elsevier BV. - 0161-813X .- 1872-9711. ; 28:6, s. 1120-1128
-
Journal article (peer-reviewed)abstract
- 2,6-Dichlorophenyl methylsulphone and a number of structurally related chemicals are CYP-activated toxicants in the olfactory mucosa in mice and rats. This toxicity involves both the olfactory neuroepithelium and its subepithelial nerves. In addition, 2,6-dichlorophenyl methylsulphone, induces glial acidic fibrillary protein expression (Gfap, a biomarker for gliosis) in the olfactory bulb, as well as long-lasting learning deficits and changes in spontaneous behavior in mice and rats. So far the 2,5-dichlorinated isomer has not been reported to cause toxicity in the olfactory system, although it gives rise to transient changes in spontaneous behavior. In the present study we used 15k cDNA gene arrays and real-time RTPCR to determine 2,6-dichlorophenyl methylsulphone-induced effects on gene expression in the olfactory bulb in mice. Seven days following a single ip dose of 2,6-dichlorophenyl methylsulphone, 56 genes were found to be differentially expressed in the olfactory bulb. Forty-one of these genes clustered into specific processes regulating, for instance, cell differentiation, cell migration and apoptosis. The genes selected for real-time RT-PCR were chosen to cover the range of B-values in the cDNA array analysis. Altered expression of Gfap, mt-Rnr2, Ncor1 and Olfml3 was confirmed. The expression of these genes was measured also in mice dosed with 2,5-dichlorophenyl methylsulphone, and mt-Rnr2 and Olfml3 were found to be altered also by this isomer. Combined with previous data, the results support the possibility that the persistent neurotoxicity induced by 2,6-dichlorophenyl methylsulphone in mice represents both an indirect and a direct effect on the brain. The 2,5-dichlorinated isomer, negative with regard to CYP-catalyzed toxicity in the olfactory mucosa, may prove useful to resolve this issue.
|
|
| 6. |
- Bruder, Carl E G, et al.
(author)
-
Phenotypically concordant and discordant monozygotic twins display different DNA copy-number-variation profiles
- 2008
-
In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 82:3, s. 763-71
-
Journal article (peer-reviewed)abstract
- The exploration of copy-number variation (CNV), notably of somatic cells, is an understudied aspect of genome biology. Any differences in the genetic makeup between twins derived from the same zygote represent an irrefutable example of somatic mosaicism. We studied 19 pairs of monozygotic twins with either concordant or discordant phenotype by using two platforms for genome-wide CNV analyses and showed that CNVs exist within pairs in both groups. These findings have an impact on our views of genotypic and phenotypic diversity in monozygotic twins and suggest that CNV analysis in phenotypically discordant monozygotic twins may provide a powerful tool for identifying disease-predisposition loci. Our results also imply that caution should be exercised when interpreting disease causality of de novo CNVs found in patients based on analysis of a single tissue in routine disease-related DNA diagnostics.
|
|
| 7. |
|
|
