Telomere Length Affects Gene Expression

Discussion of the 2009 Noble Prize in Medicine, focusing on substances that reduce telomere shortening by activating the human telomerase enzyme

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Telomere Length Affects Gene Expression

Post Number:#1  Post by ofonorow » Sun Jun 28, 2015 7:23 am



Still grinding through the Elizabeth Blackburn textbook Telomeres (2nd Edition).

I am currently reading chapter 10, Telomere Positioning Effect: Silencing Near the End. The chapter was written by Princeton professors Michelle Mondoux and Virginia Zalian, and I almost skipped the chapter because it is hard to read their writing, until I realized what these lady's are saying.

Telomere shortening doesn't only affect cell reproduction; telomere shortenning can have a global effect turning off gene expression, especially genes at the ends of chromosomes.

Whether these ladies discovered this, or their paper is only hilighting this “feature,” it explains quite a bit, (e.g. why if telomeres shorten 120 base pairs per division, the crisis can occur when telomeres are shortened to lengths of 5000 to even 8000 base pairs.)

As background, genes encode for a specific protein, usually an enzyme, and when the gene is “expressed in a cell that cell is producing that protein/enzyme. All cells have the same DNA, yet all cells are not producing all the proteins all the time. From my prior reading, the theory is that there are “binding proteins” that attach to certain genes and “turn them off” or silence them.

This is the first time reading that telomeres can have a more global effect turning off genes when they become too short. The silencing effect seems to extend to about 15,000 base pairs from the end of the telomere into the chromosome.

Backing up for a second, diet can affect gene expression too. The epigenetics field has grown out of experiments depriving female mice of certain B vitamins. The offspring produced on low B vitamins are fat and bald. Give the same mothers more of these B vitamins during pregnancy, and the offspring are lean and hairy.

If these Princeton authors are correct it might mean, for one thing, that Andrews looking for the telomerase “binding protein” may be off base. There may still be something there, but if the Terc gene (the telomerase gene) is close to the end of a chromosome, perhaps it is turned off and on due to the length of the telomeres of that particular chromosome!)

Thinking about pregnancy, the one constant during the rapid cell division is the shortening of telomeres. If this shortening does silence gene expression, then telomere shortening may be the underpinning of the differentiation process – how cells begin to differentiate into the various tissues. But I digress

The message here for us is that short telomeres can adversely affect us in multiple ways – even if the cells can still reproduce, by turning off gene expression.

And if we can lengthen them, even slowly, at some point their length alone may help our cells express telomerase.
Owen R. Fonorow
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