Passage
Each time a eukaryotic cell replicates its DNA, the telomeres at the ends of each chromosome become slightly shorter. When telomeres reach a critically short length, the cells enter the senescent state, in which cell division ceases (Figure 1) . In humans, conditions such as hypertension, liver disease, and Alzheimer disease have been associated with the decreased telomere length and resulting senescence that occur as part of the normal aging process.
Figure 1Cells that must be able to divide indefinitely (stem cells and germ cells) express an enzyme known as telomerase. Functional telomerase consists of a protein subunit called telomerase reverse transcriptase (TERT) and a noncoding RNA subunit called telomerase RNA (TR) . Using a portion of TR as a template, telomerase extends telomeres by continuously adding the sequence 5′-TTAGGG-3′ to the ends of chromosomes. The complement strand is then filled in by DNA polymerase. Telomere extension allows these cells to avoid senescence.In healthy somatic cells, however, TERT transcription is generally downregulated by the absence of the oncogene c-Myc and the presence of the tumor suppressor protein WT1. When telomerase is suppressed, the resulting critical telomere shortening has been hypothesized to prevent uncontrolled cell proliferation in adult tissues. In cancerous somatic cells, on the other hand, increased telomerase activity is often associated with tumorigenesis. WT1 is frequently absent and c-Myc is frequently overexpressed in these cells, leading to increased TERT expression.In addition to transcriptional control, TERT can be regulated at the post-transcriptional level. The TERT gene consists of 16 exons and 15 introns that can be spliced into more than 20 different isoforms in humans. Only one isoform (the active isoform) is known to extend telomeres. However, the i2 isoform, in which intron 2 is partially included in the mature mRNA (Figure 2) , has been hypothesized to downregulate residual TERT activity in somatic cells.
Figure 2
Adapted from Cifuentes-rojas C, Shippen DE. Telomerase regulation. Mutat Res. 2012;730(1-2) :20-7.
-Considering that healthy somatic cells typically transcribe the TERT gene only at low levels, where in the chromosomes of these cells is the gene most likely found?

Question

Passage
Each time a eukaryotic cell replicates its DNA, the telomeres at the ends of each chromosome become slightly shorter. When telomeres reach a critically short length, the cells enter the senescent state, in which cell division ceases (Figure 1) . In humans, conditions such as hypertension, liver disease, and Alzheimer disease have been associated with the decreased telomere length and resulting senescence that occur as part of the normal aging process.

Figure 1Cells that must be able to divide indefinitely (stem cells and germ cells) express an enzyme known as telomerase. Functional telomerase consists of a protein subunit called telomerase reverse transcriptase (TERT) and a noncoding RNA subunit called telomerase RNA (TR) . Using a portion of TR as a template, telomerase extends telomeres by continuously adding the sequence 5′-TTAGGG-3′ to the ends of chromosomes. The complement strand is then filled in by DNA polymerase. Telomere extension allows these cells to avoid senescence.In healthy somatic cells, however, TERT transcription is generally downregulated by the absence of the oncogene c-Myc and the presence of the tumor suppressor protein WT1. When telomerase is suppressed, the resulting critical telomere shortening has been hypothesized to prevent uncontrolled cell proliferation in adult tissues. In cancerous somatic cells, on the other hand, increased telomerase activity is often associated with tumorigenesis. WT1 is frequently absent and c-Myc is frequently overexpressed in these cells, leading to increased TERT expression.In addition to transcriptional control, TERT can be regulated at the post-transcriptional level. The TERT gene consists of 16 exons and 15 introns that can be spliced into more than 20 different isoforms in humans. Only one isoform (the active isoform) is known to extend telomeres. However, the i2 isoform, in which intron 2 is partially included in the mature mRNA (Figure 2) , has been hypothesized to downregulate residual TERT activity in somatic cells.

Figure 2
Adapted from Cifuentes-rojas C, Shippen DE. Telomerase regulation. Mutat Res. 2012;730(1-2) :20-7.
-Considering that healthy somatic cells typically transcribe the TERT gene only at low levels, where in the chromosomes of these cells is the gene most likely found?

Quizplus · Accepted Answer

11ecba2d_0ff6_f517_a3bf_2b3a1d24e011_MD0008_00 Gene transcription from DNA to RNA depends partly on the chromatin structure of the DNA that contains the gene. Broadly speaking, chromatin can exist in two forms: heterochromatin and euchromatin. Heterochromatin consists of DNA that is tightly coiled around histone proteins, bound by an ionic interaction between the negatively charged phosphates on the DNA backbone and positively charged lysine residues in the histone. DNA in heterochromatin is not readily accessible to RNA polymerase and so cannot be readily transcribed. Euchromatin forms when histones are modified, often by acetylation of lysine residues. The added acetyl group neutralizes the positive charge on the histone, reducing interactions between histones and DNA. The reduced interactions yield a more open form that is more accessible to RNA polymerase, allowing euchromatin to be more readily transcribed. Because somatic cells transcribe TERT at low levels, the gene that encodes TERT is most likely found in heterochromatin within these cells. In somatic cells, the TERT gene is therefore most likely in a portion of the chromosome that is tightly wound around histones. (Choice A) Relatively open, uncoiled DNA is characteristic of euchromatin. In stem cells and germ cells, the TERT gene is highly transcribed and likely to be found in euchromatin. However, this is not the case in somatic cells. (Choice B) The portion of the chromosome that interacts with the kinetochore during mitosis is the centromere. The TERT gene is unlikely to be in the centromere because the DNA of centromeres is similar to that of telomeres in that it is somewhat repetitive and encodes few genes. (Choice C) Chromosomes are found in the nucleus and do not associate with ribosomes, which are found in the cytosol and on the rough endoplasmic reticulum. It is mRNA, not chromosomes, that associates with ribosomes. Educational objective: Chromatin can be broadly classified as heterochromatin or euchromatin. Heterochromatin consists of DNA tightly coiled around histones and is not readily transcribed by RNA polymerase. Euchromatin is more loosely associated with histones and is more easily transcribed.

Passage Each Time a Eukaryotic Cell Replicates Its DNA, the Telomeres