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Telomeres don’t just protect the ends of chromosomes

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They modulate gene expressions over cells’ lifetimes.

From The Scientist :

Not only do telomeres protect the ends of chromosomes, they also modulate gene expression over cells’ lifetimes.

New work led by Jerry W. Shay and Woodring Wright of the University of Texas Southwestern Medical Center in Dallas demonstrates that telomeres are more than just buffer zones. The team found that as chromosomes fold within the nucleus, telomeres come into contact with faraway genes and alter their expression. As telomeres shorten, which happens with aging, chromosome looping and gene-expression patterns change.

“I’m delighted with this evidence that the [telomere] sequence may actually be doing some regulation and that the decrease of the sequence in some cells may drastically affect the way they are behaving,” says Mary-Lou Pardue, who studies telomeres at MIT and was not involved in the research. She points out that telomeres are longer and have a more complex sequence than should be necessary to simply protect the chromosome ends. More.

Here’s the abstract:

While global chromatin conformation studies are emerging, very little is known about the chromatin conformation of human telomeres. Most studies have focused on the role of telomeres as a tumor suppressor mechanism. Here we describe how telomere length regulates gene expression long before telomeres become short enough to produce a DNA damage response (senescence). We directly mapped the interactions adjacent to specific telomere ends using a Hi-C (chromosome capture followed by high-throughput sequencing) technique modified to enrich for specific genomic regions. We demonstrate that chromosome looping brings the telomere close to genes up to 10 Mb away from the telomere when telomeres are long and that the same loci become separated when telomeres are short. Furthermore, expression array analysis reveals that many loci, including noncoding RNAs, may be regulated by telomere length. We report three genes (ISG15 [interferon-stimulated gene 15 kd], DSP [Desmoplakin], and C1S [complement component 1s subcomplement]) located at three different subtelomeric ends (1p, 6p, and 12p) whose expressions are altered with telomere length. Additionally, we confirmed by in situ analysis (3D-FISH [three-dimensional fluorescence in situ hybridization]) that chromosomal looping occurs between the loci of those genes and their respective telomere ends. We term this process TPE-OLD for “telomere position effect over long distances.” Our results suggest a potential novel mechanism for how telomere shortening could contribute to aging and disease initiation/progression in human cells long before the induction of a critical DNA damage response. – J.D. Robin et al., “Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances,” Genes Dev, 28:2464-76, 2014. .pdf

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From The Scientist :

Not only do telomeres protect the ends of chromosomes, they also modulate gene expression over cells’ lifetimes.

New work led by Jerry W. Shay and Woodring Wright of the University of Texas Southwestern Medical Center in Dallas demonstrates that telomeres are more than just buffer zones. The team found that as chromosomes fold within the nucleus, telomeres come into contact with faraway genes and alter their expression. As telomeres shorten, which happens with aging, chromosome looping and gene-expression patterns change.

“I’m delighted with this evidence that the [telomere] sequence may actually be doing some regulation and that the decrease of the sequence in some cells may drastically affect the way they are behaving,” says Mary-Lou Pardue, who studies telomeres at MIT and was not involved in the research. She points out that telomeres are longer and have a more complex sequence than should be necessary to simply protect the chromosome ends. More.

Here’s the abstract:

While global chromatin conformation studies are emerging, very little is known about the chromatin conformation of human telomeres. Most studies have focused on the role of telomeres as a tumor suppressor mechanism. Here we describe how telomere length regulates gene expression long before telomeres become short enough to produce a DNA damage response (senescence). We directly mapped the interactions adjacent to specific telomere ends using a Hi-C (chromosome capture followed by high-throughput sequencing) technique modified to enrich for specific genomic regions. We demonstrate that chromosome looping brings the telomere close to genes up to 10 Mb away from the telomere when telomeres are long and that the same loci become separated when telomeres are short. Furthermore, expression array analysis reveals that many loci, including noncoding RNAs, may be regulated by telomere length. We report three genes (ISG15 [interferon-stimulated gene 15 kd], DSP [Desmoplakin], and C1S [complement component 1s subcomplement]) located at three different subtelomeric ends (1p, 6p, and 12p) whose expressions are altered with telomere length. Additionally, we confirmed by in situ analysis (3D-FISH [three-dimensional fluorescence in situ hybridization]) that chromosomal looping occurs between the loci of those genes and their respective telomere ends. We term this process TPE-OLD for “telomere position effect over long distances.” Our results suggest a potential novel mechanism for how telomere shortening could contribute to aging and disease initiation/progression in human cells long before the induction of a critical DNA damage response. – J.D. Robin et al., “Telomere position effect: regulation of gene expression with progressive telomere shortening over long distances,” Genes Dev, 28:2464-76, 2014. .pdf

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Comments
Function everywhere!!!!Andre
March 11, 2015
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