Replication Timing Profile Reflects the Distinct Functional and Genomic Features of the MHC Class II Region

Takousis, Petros; Johonnett, Peter; Williamson, Jon; Sasieni, Peter; Warnes, Gary; Forshew, Tim; Azuara, Véronique; Fisher, Amanda G.; Wu, Peili; Jones, Tania; Vatcheva, Radost; Beck, Stephan; Sheer, Denise

doi:10.4161/cc.6.19.4762

Cited by 5 publications

(3 citation statements)

References 31 publications

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“…Some specific associations of chromosome territories with nuclear proteins were invoked [166]. An open chromatin configuration has been described in relation to the timing of DNA replication for the MHC which occurred early in S-phase [167]. The generation of a 2 kb resolution tiling path MHC array [168] has also allowed chromatin profiling and identification of cell-specific genomic anchors which show dynamic changes on transcriptional activation [169].…”

Section: Genetical Genomics and Modulation Of Gene Expression In The Mhcmentioning

confidence: 99%

The human Major Histocompatibility Complex as a paradigm in genomics research

Vandiedonck¹,

Knight²

2009

Briefings in Functional Genomics and Proteomics

109

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Since its discovery more than 50 years ago, the human Major Histocompatibility Complex (MHC) on chromosome 6p21.3 has been at the forefront of human genetic research. Here, we review from a historical perspective the major advances in our understanding of the nature and consequences of genetic variation which have involved the MHC, as well as highlighting likely future directions. As a consequence of its particular genomic structure, its remarkable polymorphism and its early implication in numerous diseases, the MHC has been considered as a model region for genomics, being the first substantial region to be sequenced and establishing fundamental concepts of linkage disequilibrium, haplotypic structure and meiotic recombination. Recently, the MHC became the first genomic region to be entirely re-sequenced for common haplotypes, while studies mapping gene expression phenotypes across the genome have strongly implicated variation in the MHC. This review shows how the MHC continues to provide new insights and remains in the vanguard of contemporary research in human genomics.

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Section: Genetical Genomics and Modulation Of Gene Expression In The Mhcmentioning

confidence: 99%

The human Major Histocompatibility Complex as a paradigm in genomics research

Vandiedonck¹,

Knight²

2009

Briefings in Functional Genomics and Proteomics

109

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“…The MHC cluster is subject to unusual replication timing control and exists in a relatively open chromatin conformation [Takousis et al, 2007]. Matrix attachment regions (MARs), which are rich in AT tracts and repetitive sequences, are located throughout the MHC.…”

Section: Discussionmentioning

confidence: 99%

Analysis of Segmental Duplications, Mouse Genome Synteny and Recurrent Cancer-Associated Amplicons in Human Chromosome 6p21–p12

Martin

Yoshimoto²,

Ludkovski³

et al. 2010

Cytogenet Genome Res

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It has been proposed that regions of microhomology in the human genome could facilitate genomic rearrangements, copy number transitions, and rapid genomic change during tumor progression. To investigate this idea, this study examines the role of repetitive sequence elements, and corresponding syntenic mouse genomic features, in targeting cancer-associated genomic instability of specific regions of the human genome. Automated database-mining algorithms designed to search for frequent copy number transitions and genomic breakpoints were applied to 2 publicly-available online databases and revealed that 6p21–p12 is one of the regions of the human genome most frequently involved in tumor-specific alterations. In these analyses, 6p21–p12 exhibited the highest frequency of genomic amplification in osteosarcomas. Analysis of repetitive elements in regions of homology between human chromosome 6p and the syntenic regions of the mouse genome revealed a strong association between the location of segmental duplications greater than 5 kilobase-pairs and the position of discontinuities at the end of the syntenic region. The presence of clusters of segmental duplications flanking these syntenic regions also correlated with a high frequency of amplification and genomic alteration. Collectively, the experimental findings, in silico analyses, and comparative genomic studies presented here suggest that segmental duplications may facilitate cancer-associated copy number transitions and rearrangements at chromosome 6p21–p12. This process may involve homology-dependent DNA recombination and/or repair, which may also contribute towards the overall plasticity of the human genome.

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“…The higher but less plastic level of chromatin organization seems to have a biological function. Thus, due to the location of genes of the major histo compatibility complex (MHC) class II region in an AT rich isochore, it is assumed that open chromatin confrontation supported by appropriate RD in differ ent types of cells protects the human body from patho gens efficiently [15]. The same procedure may be applied in the case of the human chromosome band 9p22, which contains a cascade of different interferon genes, including the IFNA2 gene [16].…”

Section: Introductionmentioning

confidence: 99%

Differential activity of DNA replication origins located on the human chromosome band 9p22

Kholodii

Tarantul

2015

Mol. Genet. Microbiol. Virol.

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There is scanty knowledge concerning initiation activity of cell type specific DNA replication ori gins (oris) subject to regulation during development. At the same time, the knowledge on the subject can serve as an important reference for both the epigenetic developmental program revealing and identifying the fea tures of this program in the course of development. Here we attempted to extend our knowledge on the sub ject on the example of the IFNA2 locus oris located in an AT rich isochore on the human chromosome band 9p22. By Q PCR, we measured the activity of two oris in cell lines originating from epithelium of the cervix (HeLa) and the early precursor of neuronal cell (HEK 293), and compared with their activity in an immor talized fibroblast cell line (CH). Using these three lines as a model, we have demonstrated for the first time the great epigenetic plasticity of oris located in a mammalian genetic locus (IFNA2). Therefore, this locus can be recommended as a convenient model for studying the epigenetic regulation of DNA replication.

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Replication Timing Profile Reflects the Distinct Functional and Genomic Features of the MHC Class II Region

Cited by 5 publications

References 31 publications

The human Major Histocompatibility Complex as a paradigm in genomics research

The human Major Histocompatibility Complex as a paradigm in genomics research

Analysis of Segmental Duplications, Mouse Genome Synteny and Recurrent Cancer-Associated Amplicons in Human Chromosome 6p21–p12

Differential activity of DNA replication origins located on the human chromosome band 9p22

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