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Chromatin remodeling of human subtelomeres and TERRA promoters upon cellular senescence: commonalities and differences between chromosomes.

ABSTRACT: Subtelomeres are patchworks of evolutionary conserved sequence blocks and harbor the transcriptional start sites for telomere repeat containing RNAs (TERRA). Recent studies suggest that the interplay between telomeres and subtelomeric chromatin is required for maintaining telomere function. To further characterize chromatin remodeling of subtelomeres in relation to telomere shortening and cellular senescence, we systematically quantified histone modifications and DNA methylation at the subtelomeres of chromosomes 7q and 11q in primary human WI-38 fibroblasts. Upon senescence, both subtelomeres were characterized by a decrease in markers of constitutive heterochromatin, suggesting relative chromatin relaxation. However, we did not find increased levels of markers of euchromatin or derepression of the 7q VIPR2 gene. The repressed state of the subtelomeres was maintained upon senescence, which could be attributed to a rise in levels of facultative heterochromatin markers at both subtelomeres. While senescence-induced subtelomeric chromatin remodeling was similar for both chromosomes, chromatin remodeling at TERRA promoters displayed chromosome-specific patterns. At the 7q TERRA promoter, chromatin structure was co-regulated with the more proximal subtelomere. In contrast, the 11q TERRA promoter, which was previously shown to be bound by CCCTC-binding factor CTCF, displayed lower levels of markers of constitutive heterochromatin that did not change upon senescence, whereas levels of markers of facultative heterochromatin decreased upon senescence. In line with the chromatin state data, transcription of 11q TERRA but not 7q TERRA was detected. Our study provides a detailed description of human subtelomeric chromatin dynamics and shows distinct regulation of the TERRA promoters of 7q and 11q upon cellular senescence.

SUBMITTER: Thijssen PE

PROVIDER: S-EPMC3741221 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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Chromatin remodeling of human subtelomeres and TERRA promoters upon cellular senescence: commonalities and differences between chromosomes.

Thijssen Peter E PE Tobi Elmar W EW Balog Judit J Schouten Suzanne G SG Kremer Dennis D El Bouazzaoui Fatiha F Henneman Peter P Putter Hein H Eline Slagboom P P Heijmans Bastiaan T BT van der Maarel Silvère M SM

Epigenetics 20130417 5

Subtelomeres are patchworks of evolutionary conserved sequence blocks and harbor the transcriptional start sites for telomere repeat containing RNAs (TERRA). Recent studies suggest that the interplay between telomeres and subtelomeric chromatin is required for maintaining telomere function. To further characterize chromatin remodeling of subtelomeres in relation to telomere shortening and cellular senescence, we systematically quantified histone modifications and DNA methylation at the subtelome ...[more]

PMID: 23644601

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Project description:Assembly of a complete Y chromosome is a significant challenge in animals with an XX/XY sex-determination system. Recently, we created YY-supermale yellow catfish by crossing XY males with sex-reversed XY females, providing a valuable model for Y-chromosome assembly and evolution. Here, we assembled highly homomorphic Y and X chromosomes by sequencing genomes of the YY supermale and XX female in yellow catfish, revealing their nucleotide divergences with only less than 1% and with the same gene compositions. The sex-determining region (SDR) was identified to locate within a physical distance of 0.3 Mb by FST scanning. Strikingly, the incipient sex chromosomes were revealed to originate via autosome-autosome fusion and were characterized by a highly rearranged region with an SDR downstream of the fusion site. We found that the Y chromosome was at a very early stage of differentiation, as no clear evidence of evolutionary strata and classical structure features of recombination suppression for a rather late stage of Y-chromosome evolution were observed. Significantly, a number of sex-antagonistic mutations and the accumulation of repetitive elements were discovered in the SDR, which might be the main driver of the initial establishment of recombination suppression between young X and Y chromosomes. Moreover, distinct three-dimensional chromatin organizations of the Y and X chromosomes were identified in the YY supermales and XX females, as the X chromosome exhibited denser chromatin structure than the Y chromosome, while they respectively have significantly spatial interactions with female- and male-related genes compared with other autosomes. The chromatin configuration of the sex chromosomes as well as the nucleus spatial organization of the XX neomale were remodeled after sex reversal and similar to those in YY supermales, and a male-specific loop containing the SDR was found in the open chromatin region. Our results elucidate the origin of young sex chromosomes and the chromatin remodeling configuration in the catfish sexual plasticity.

Dataset Information

Chromatin remodeling of human subtelomeres and TERRA promoters upon cellular senescence: commonalities and differences between chromosomes.

Publications

Chromatin remodeling of human subtelomeres and TERRA promoters upon cellular senescence: commonalities and differences between chromosomes.

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