Long-range telomere regulation of gene expression: Telomere looping and telomere position effect over long distances (TPE-OLD).

Long-range telomere regulation of gene expression: Telomere looping and telomere position effect over long distances (TPE-OLD). Differentiation. 2017 Nov 22;99:1-9 Authors: Kim W, Shay JW Abstract The human cellular reverse transcriptase, telomerase, is very tightly regulated in large long-lived species. Telomerase is expressed during early human fetal development, is turned off in most adult tissues, and then becomes reactivated in almost all human cancers. However, the exact mechanism regulating these switches in expression are not known. We recently described a phenomenon where genes are regulated by telomere length dependent loops (telomere position effects over long distances; TPE-OLD). The hTERT gene is ~ 1.2Mb from the human chromosome 5p end. We observed that when telomeres are long hTERT gene expression is repressed and a probe next to the 5p telomere and the hTERT locus are spatially co-localized. When telomeres are short at least one of the hTERT alleles is spatially separated from the telomere, developing more active histone marks and changes in DNA methylation in the hTERT promoter region. These findings have implications for how cells turn off telomerase when telomeres are long during fetal development and how cancer cells reactivate telomerase in cells that have short telomeres. In addition to TPE-OLD, in proliferating stem cells such as activated T-lymphocytes, telomerase can be reversibly activated and silenced by te...
Source: Differentiation - Category: Research Authors: Tags: Differentiation Source Type: research