Gene duplication in the epigenomic era: Roles of chromatin modifications

Zheng, Deyou

doi:10.4161/epi.3.5.6991

Cited by 3 publications

(2 citation statements)

References 31 publications

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“…However, the duplicated genes we analyzed are on average very far away and sometimes even on different chromosomes. The conservation of epigenetic modification is in contradiction to the results presented by a study on segmental duplications in which an asymmetry was observed in the methylation level and in the histone acetylation that could be linked to pseudogenization [80]. Although in this last study, the genes considered may not all be pseudogenes, the discrepancy could be explained by the fact that in our work, we focused only on duplicated genes that are both functional.…”

Section: Discussioncontrasting

confidence: 86%

Does the Presence of Transposable Elements Impact the Epigenetic Environment of Human Duplicated Genes?

Lannes

Rizzon

Lerat

2019

Genes

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Epigenetic modifications have an important role to explain part of the intra- and inter-species variation in gene expression. They also have a role in the control of transposable elements (TEs) whose activity may have a significant impact on genome evolution by promoting various mutations, which are expected to be mostly deleterious. A change in the local epigenetic landscape associated with the presence of TEs is expected to affect the expression of neighboring genes since these modifications occurring at TE sequences can spread to neighboring sequences. In this work, we have studied how the epigenetic modifications of genes are conserved and what the role of TEs is in this conservation. For that, we have compared the conservation of the epigenome associated with human duplicated genes and the differential presence of TEs near these genes. Our results show higher epigenome conservation of duplicated genes from the same family when they share similar TE environment, suggesting a role for the differential presence of TEs in the evolutionary divergence of duplicates through variation in the epigenetic landscape.

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Section: Discussioncontrasting

confidence: 86%

Does the Presence of Transposable Elements Impact the Epigenetic Environment of Human Duplicated Genes?

Lannes

Rizzon

Lerat

2019

Genes

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“…In this regard, it is important to mention that common breakpoints found in the rearrangement of distal LCR22 blocks in two patients [38] is located to one of the highly active subunits identified in this study (the subunit in red color at the end of the first duplication group in Figure 2B), supporting that our map of duplications could be useful for studying human genomic disorders. Some interesting directions to further explore our findings are, (i) Alu sequences may be preferential sites of double strand breakage after homology based alignment [14], and (ii) chromatin modification in the vicinity of Alu sequences may make a region prone for duplications as local chromatin structure (e.g., accessibility) is an important factor influencing DNA duplication and its subsequent evolution [19,39]. Along the same line, we should note here that AluY insertion sites have been reported to show elevated recombination rates [40].…”

Section: Discussionmentioning

confidence: 99%

Characterization of the past and current duplication activities in the human 22q11.2 region

et al. 2011

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BackgroundSegmental duplications (SDs) on 22q11.2 (LCR22), serve as substrates for meiotic non-allelic homologous recombination (NAHR) events resulting in several clinically significant genomic disorders.ResultsTo understand the duplication activity leading to the complicated SD structure of this region, we have applied the A-Bruijn graph algorithm to decompose the 22q11.2 SDs to 523 fundamental duplication sequences, termed subunits. Cross-species syntenic analysis of primate genomes demonstrates that many of these LCR22 subunits emerged very recently, especially those implicated in human genomic disorders. Some subunits have expanded more actively than others, and young Alu SINEs, are associated much more frequently with duplicated sequences that have undergone active expansion, confirming their role in mediating recombination events. Many copy number variations (CNVs) exist on 22q11.2, some flanked by SDs. Interestingly, two chromosome breakpoints for 13 CNVs (mean length 65 kb) are located in paralogous subunits, providing direct evidence that SD subunits could contribute to CNV formation. Sequence analysis of PACs or BACs identified extra CNVs, specifically, 10 insertions and 18 deletions within 22q11.2; four were more than 10 kb in size and most contained young AluYs at their breakpoints.ConclusionsOur study indicates that AluYs are implicated in the past and current duplication events, and moreover suggests that DNA rearrangements in 22q11.2 genomic disorders perhaps do not occur randomly but involve both actively expanded duplication subunits and Alu elements.

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DNA Methylation and Histone Modification Profiles of Mouse Organic Anion Transporting Polypeptides

et al. 2012

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Organic anion transporting polypeptides (rodents, Oatps; human, OATPs) are primarily involved in the transmembrane transportation of a wide range of endogenous and exogenous compounds. Multiple mouse Oatp1 isoforms are closely located on chromosome 6, where each isoform shows distinct tissue distribution; Oatp1b2, Oatp1a6, and Oatp1c1 are expressed exclusively in the liver, kidney, and cerebrum, respectively; Oatp1a1 in the liver and kidney; and Oatp1a4 in the liver and cerebrum. We have identified tissue-dependent differentially methylated region (T-DMR) around the transcriptional start site (TSS) of Oatp1b2, which correlates with its liver-specific expression. Bisulfite sequencing also demonstrated the presence of T-DMRs around the TSS in other Oatp1 genes: CpG dinucleotides at +149 relative to the TSS for Oatp1c1; 248, +101, and +356 for Oatp1a4; 2572 and 2550 for Oatp1a1; and 2122 and +216 for Oatp1a6 were differentially methylated among the liver, kidney, and cerebrum. These methylation profiles were largely consistent with the tissue distribution of Oatp1 mRNAs. Chromatin immunoprecipitation assay revealed that the mRNA expression of Oatp1 genes was accompanied by acetylated histone H3. Human OATP1B1 and OATP1B3 are located on chromosome 12p12 in the OATP1 cluster; both show predominant expression in the liver. These genes also contained T-DMRs that were hypomethylated in the liver, compared with kidney cortex: 2511, 2411, and +92 relative to the TSS for OATP1B1 and 2331, +70, and +73 for OATP1B3. These results suggest that the difference in epigenetic profiles comprising DNA methylation and histone acetylation determines the distinct tissue distribution of Oatp/OATP mRNAs.

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Gene duplication in the epigenomic era: Roles of chromatin modifications

Cited by 3 publications

References 31 publications

Does the Presence of Transposable Elements Impact the Epigenetic Environment of Human Duplicated Genes?

Does the Presence of Transposable Elements Impact the Epigenetic Environment of Human Duplicated Genes?

Characterization of the past and current duplication activities in the human 22q11.2 region

DNA Methylation and Histone Modification Profiles of Mouse Organic Anion Transporting Polypeptides

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