Regulation of HTERT
The hTERT gene, located on chromosome 5, consists of 16 exons and 15 introns spanning 35kb. The core promoter of hTERT includes 330 base pairs upstream of the translation start site (ATG), as well as 37 base pairs of exon 2 of the hTERT gene. The hTERT promoter is GC-rich and lacks TATA and CAAT boxes but contains many sites for several transcription factors giving indication of a high level of regulation by multiple factors in many cellular contexts. Transcription factors which can activate hTERT include many oncogenes (cancer causing genes) such as c-Myc, Sp1, HIF-1, AP2, Estrogen receptor and many more, while many cancer suppressing genes such as p53, WT1 and Menin produce factors which suppress hTERT activity . Another form of up-regulation is through demethylation of histones proximal to the promoter region, imitating the low density of trimethylated histones seen in embryonic stem cells. This allows for the recruitment of histone acetyltransferase (HAT) to unwind the sequence allowing for transcription of the gene.
Telomere deficiency is often linked to aging, cancers and the conditions dyskeratosis congenita (DKC) and Cri du chat. Meanwhile, over-expression of hTERT is often associated with cancers and tumor formation. The regulation of hTERT is extremely important to the maintenance of stem and cancer cells and can be used in multiple ways in the field of regenerative medicine.
Read more about this topic: Telomerase Reverse Transcriptase
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