# Repression of hTERT gene during cell differentiation

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2020 · $328,116

## Abstract

Abstract
 Our long-term goal is to determine the mechanisms of telomerase regulation during
development. The hTERT gene, encoding the limiting subunit of human telomerase, is primarily
regulated at the level of transcription. It is highly expressed in pluripotent stem cells, but
stringently repressed in most somatic cells. Regulation of transcription during development and
differentiation often involves distal elements and chromatin reorganization, in addition to
proximal promoter elements. We previously showed that the endogenous hTERT locus was
embedded in a condensed chromatin domain in many somatic cells. Consistent with the vital
role of chromatin in its tight regulation, we found that an episomal hTERT locus in human
fibroblasts was not subjected to repression, whereas a chromosomally integrated hTERT locus
recapitulated its native regulation. To study the mechanisms of hTERT repression, we
developed a novel technical platform, the recombinase-mediated BAC targeting or RMBT
method, for targeted integration of single-copy BAC reporters into specified chromosomal sites.
This technique enables us to study the regulation of hTERT gene in its native genomic context.
Here, we hypothesize that 1) the interplay between distal elements and core promoter in their
native chromatin contexts is important for hTERT repression in somatic cells and reactivation in
cancer cells; and 2) polymorphic regulatory elements of the hTERT gene impact human aging
and tumorigenesis. We propose three specific aims: 1) determine the recruitment of corepressor
complexes and their roles in hTERT repression; 2) determine the regulation of hTERT promoter
by Ets family proteins in normal and cancer cells; 3) determine the function and genetic variation
of a polymorphic element in hTERT regulation and human longevity.

## Key facts

- **NIH application ID:** 9962156
- **Project number:** 5R01GM071725-14
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** JIYUE ZHU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $328,116
- **Award type:** 5
- **Project period:** 2004-08-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9962156

## Citation

> US National Institutes of Health, RePORTER application 9962156, Repression of hTERT gene during cell differentiation (5R01GM071725-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9962156. Licensed CC0.

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