Human centromeric DNAs

Lee, C.; Wevrick, Rachel; Fisher, Richard; Ferguson‐Smith, Malcolm A.; Lin, Chyi-Chyang

doi:10.1007/s004390050508

Cited by 221 publications

(176 citation statements)

References 147 publications

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“…The same motif prediction analysis also identified sequences derived from a consensus consisting of repetitions of the CCATT pentamer [32], which is found in human peri-centromeric satellite 2/3 sequences, and were identified in three additional peaks ( Figure 4A and 4C, Supplementary information, Table S1). The three remaining peaks represented two alphoid satellite sequences and one LINE L1 sequence ( Figure 4D, Supplementary information, Table S1).…”

Section: A Subset Of Trf Binding Sites Correspond To Nontelomeric Satmentioning

confidence: 62%

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Simonet¹,

Zaragosi²,

Philippe³

et al. 2011

Cell Res

140

146

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The study of the proteins that bind to telomeric DNA in mammals has provided a deep understanding of the mechanisms involved in chromosome-end protection. However, very little is known on the binding of these proteins to nontelomeric DNA sequences. The TTAGGG DNA repeat proteins 1 and 2 (TRF1 and TRF2) bind to mammalian telomeres as part of the shelterin complex and are essential for maintaining chromosome end stability. In this study, we combined chromatin immunoprecipitation with high-throughput sequencing to map at high sensitivity and resolution the human chromosomal sites to which TRF1 and TRF2 bind. While most of the identified sequences correspond to telomeric regions, we showed that these two proteins also bind to extratelomeric sites. The vast majority of these extratelomeric sites contains interstitial telomeric sequences (or ITSs). However, we also identified non-ITS sites, which correspond to centromeric and pericentromeric satellite DNA. Interestingly, the TRF-binding sites are often located in the proximity of genes or within introns. We propose that TRF1 and TRF2 couple the functional state of telomeres to the long-range organization of chromosomes and gene regulation networks by binding to extratelomeric sequences.

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Section: A Subset Of Trf Binding Sites Correspond To Nontelomeric Satmentioning

confidence: 62%

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Simonet¹,

Zaragosi²,

Philippe³

et al. 2011

Cell Res

140

146

View full text Add to dashboard Cite

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“…These multi-copy sequences largely represent interchromosomal duplications, inhibiting chromosome-specific contig assignment extending into centromeric regions (She et al 2004). Additionally, alpha satellite is commonly found adjacent to other satellite families, including classical human satellite families (HSAT I, II, and III) and beta and gamma satellites, each defined by their respective individual sequence composition and evolution (Lee et al 1997;Warburton et al 2008). In some cases, these adjacent, smaller satellite arrays within the centromeric transition regions can be traversed by paired reads and standard assembly and are included in the reference sequence (She et al 2004;Warburton et al 2008), yet larger arrays of satellites, such as HSAT II and III, encompass millions of bases that are difficult to distinguish between chromosomal subsets, thereby limiting assembly efforts to reach alpha satellite.…”

Section: A Genomic Model Of Human Centromeresmentioning

confidence: 99%

Human centromere genomics: now it's personal

Hayden

2012

Chromosome Res

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Advances in human genomics have accelerated studies in evolution, disease, and cellular regulation. However, centromere sequences, defining the chromosomal interface with spindle microtubules, remain largely absent from ongoing genomic studies and disconnected from functional, genome-wide analyses. This disparity results from the challenge of predicting the linear order of multi-megabase-sized regions that are composed almost entirely of nearidentical satellite DNA. Acknowledging these challenges, the field of human centromere genomics possesses the potential to rapidly advance given the availability of individual, or personalized, genome projects matched with the promise of long-read sequencing technologies. Here I review the current genomic model of human centromeres in consideration of those studies involving functional datasets that examine the role of sequence in centromere identity.

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“…Repetitive (ATTCCATTCG) 2 DNA sequence is highly represented in regions localized in the pericentromere of chromosome 1 and 16, named satellite 2 [30,31]. The methylation status of satellite 2 sequences was investigated by a methylation-sensitive endonuclease-based assay revealing decreased CpG methylation levels in two primary malignant mesothelioma cellular populations (MES-SS 01, MES-PR 99) and in H28 immortalized MPM cell line, if compared with normal mesothelial cells (HMC2) (Fig.…”

Section: Satellite 2 Pericentromeric Dna Hypomethylation and Dnmts Almentioning

confidence: 99%

Decitabine, differently from DNMT1 silencing, exerts its antiproliferative activity through p21 upregulation in malignant pleural mesothelioma (MPM) cells

et al. 2009

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a b s t r a c tMalignant pleural mesothelioma (MPM) is a locally aggressive neoplasm, principally linked to asbestos fibres exposure. Strong evidences associate this pollutant with induction of DNA breaks, aberrant chromosomes segregation and important chromosomal rearrangements, considered crucial events in malignant transformation. A considerable contribution to cellular transformation in MPM is also given by the presence of high genomic instability, as well as by the increased DNA methylation, and consequent decreased expression, of tumor-suppressor genes. In this study we first demonstrated that MPM cells are characterized by a decreased methylation level of pericentromeric DNA sequences which can justify, at least in part, the genomic instability observed in this neoplasia. Concomitantly, we found a paradoxical increased expression of DNMT1, the most expressed DNA methyltransferases in MPM cells, DNMT3a and all five isoforms of DNMT3b. Thus, we compared two experimental strategies, DNMT1 silencing and usage of a demethylating agent (5-aza-2 -deoxycytidine or Decitabine), both theoretically able to revert the locally hypermethylated phenotype and considered potential future therapeutic approaches for MPM. Interestingly, both strategies substantially decrease cell survival of MPM cells but the antitumor activity of Decitabine, differently from DNMT1 silencing, is mediated, at least in part, by a p53-independent p21 upregulation, and is characterized by the arrest of MPM cells at the G2/M phase of the cell cycle. These results indicate that the two approaches act probably through different mechanisms and, thus, that DNMT1 silencing can be considered an effective alternative to Decitabine for cancer treatment.

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Human centromeric DNAs

Cited by 221 publications

References 147 publications

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

The human TTAGGG repeat factors 1 and 2 bind to a subset of interstitial telomeric sequences and satellite repeats

Human centromere genomics: now it's personal

Decitabine, differently from DNMT1 silencing, exerts its antiproliferative activity through p21 upregulation in malignant pleural mesothelioma (MPM) cells

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