Molecular and Cellular Evidence for the Alternative Lengthening of Telomeres (ALT) Mechanism in Chicken

O'Hare, Thomas H.; Delany, Mary E.

doi:10.1159/000330125

Cited by 13 publications

(13 citation statements)

References 97 publications

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“…The 4-day-old embryos of AA broilers and DF-1 cells (a non-transformed, immortalized, telomerase-negative chicken embryo fibroblast cell line) were used as positive and negative controls, respectively. Consistent with published studies [ 34 , 44 ], the 4-day-old embryos exhibited high expression of both chTERT and chTR, and DF-1 cells exhibited very low expression or no expression of chTERT and chTR ( Fig 3A ). The PCPs showed no expression of chTERT but low expression of chTR, which was similar to observations in telomerase-negative CEFs [ 44 ].…”

Section: Resultssupporting

confidence: 92%

Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR

Wang¹,

Zhang

et al. 2017

PLoS ONE

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The chicken is an important agricultural animal and model for developmental biology, immunology and virology. Excess fat accumulation continues to be a serious problem for the chicken industry. However, chicken adipogenesis and obesity have not been well investigated, because no chicken preadipocyte cell lines have been generated thus far. Here, we successfully generated two immortalized chicken preadipocyte cell lines through transduction of either chicken telomerase reverse transcriptase (chTERT) alone or in combination with chicken telomerase RNA (chTR). Both of these cell lines have survived >100 population doublings in vitro, display high telomerase activity and have no sign of replicative senescence. Similar to primary chicken preadipocytes, these two cell lines display a fibroblast-like morphology, retain the capacity to differentiate into adipocytes, and do not display any signs of malignant transformation. Isoenzyme analysis and PCR-based analysis confirmed that these two cell lines are of chicken origin and are free from inter-species contamination. To our knowledge, this is the first report demonstrating the generation of immortal chicken cells by introduction of chTERT and chTR. Our established chicken preadipocyte cell lines show great promise as an in vitro model for the investigation of chicken adipogenesis, lipid metabolism, and obesity and its related diseases, and our results also provide clues for immortalizing other avian cell types.

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Section: Resultssupporting

confidence: 92%

Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR

Wang¹,

Zhang

et al. 2017

PLoS ONE

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“…The experiments were performed with primary CEFs and the immortal DF1 fibroblast cell line. DF1 cells use the ALT method to maintain telomere length (26,47,56). Primary CEFs cultured for 5 days and DF1 cells express very-low-level or no telomerase activity.…”

Section: Resultsmentioning

confidence: 99%

Alternatively Spliced Telomerase Reverse Transcriptase Variants Lacking Telomerase Activity Stimulate Cell Proliferation

Hrdličková

Nehyba

Bose

2012

Molecular and Cellular Biology

115

138

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Eight human and six chicken novel alternatively spliced (AS) variants of telomerase reverse transcriptase (TERT) were identified, including a human variant (⌬4-13) containing an in-frame deletion which removed exons 4 through 13, encoding the catalytic domain of telomerase. This variant was expressed in telomerase-negative normal cells and tissues as well as in transformed telomerase-positive cell lines and cells which employ an alternative method to maintain telomere length. The overexpression of the ⌬4-13 variant significantly elevated the proliferation rates of several cell types without enhancing telomerase activity, while decreasing the endogenous expression of this variant by use of small interfering RNA (siRNA) technology reduced cell proliferation. The expression of the ⌬4-13 variant stimulated Wnt signaling. In chicken cells, AS TERT variants containing internal deletions or insertions that eliminated or reduced telomerase activity also enhanced cell proliferation. This is the first report that naturally occurring AS TERT variants which lack telomerase activity stimulate cell proliferation.

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“…Elevated TERT expression contributes to telomerase-dependent maintenance of telomeres that is often required for long-term proliferation and survival of cancer cells [ 11 ]. Similar phenotypes can be achieved through a telomerase-independent process, known as alternative lengthening of telomeres (ALT), which has been observed in both humans [ 12 , 13 ] and chickens [ 14 ]. Expression of TERT is tightly regulated through many mechanisms, including epigenetic modification of the promoter region to regulate telomerase activity in most somatic cells [ 15 , 16 ].…”

Section: Introductionmentioning

confidence: 98%

ALV Integration-Associated Hypomethylation at the TERT Promoter Locus

Lam

Beemon

2018

Viruses

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Avian leukosis virus (ALV) is a simple retrovirus that can induce B-cell lymphoma in chicken(s) and other birds by insertional mutagenesis. The promoter region of telomerase reverse transcriptase (TERT) has been identified as an important integration site for tumorigenesis. Tumors with TERT promoter integrations are associated with increased TERT expression. The mechanism of this activation is still under investigation. We asked whether insertion of proviral DNA perturbs the epigenome of the integration site and, subsequently, impacts the regulation of neighboring genes. DNA cytosine methylation, which generally acts to suppress transcription, is one major form of epigenetic regulation. In this study, we examine allele-specific methylation patterns of genomic DNA from chicken tumors by bisulfite sequencing. We observed that alleles with TERT promoter integrations are associated with decreased methylation in the host genome near the site of integration. Our observations suggest that insertion of ALV in the TERT promoter region may induce expression of TERT through inhibition of maintenance methylation in the TERT promoter region.

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Molecular and Cellular Evidence for the Alternative Lengthening of Telomeres (ALT) Mechanism in Chicken

Cited by 13 publications

References 97 publications

Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR

Immortalization of chicken preadipocytes by retroviral transduction of chicken TERT and TR

Alternatively Spliced Telomerase Reverse Transcriptase Variants Lacking Telomerase Activity Stimulate Cell Proliferation

ALV Integration-Associated Hypomethylation at the TERT Promoter Locus

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