# Regulation of developmental potency by the transposon LINE1

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2020 · $388,325

## Abstract

SUMMARY/ABSTRACT
Understanding the molecular regulation of early mammalian development is of fundamental importance and
may inform new therapeutic avenues in Reproductive Health and Regenerative Medicine. Our knowledge of
early development is very limited and largely derived from studies of single copy protein-coding genes.
However, single copy protein-coding genes comprise only a minor fraction (~2%) of our genome. About half of
the mouse and human genomes is derived from Transposable Elements (TEs), which are sequences repeated
throughout the chromosomes and in some cases capable of moving to different locations in the genome.
Despite being generally silenced in differentiated cell types, certain classes of TEs are highly expressed in
mouse and human pre-implantation embryos and pluripotent stem cells. The role of TEs in early mammalian
development remains essentially unknown. Our preliminary data in mouse embryonic stem cells and embryos
support a new model in which the alternative transcriptional programs of totipotency and pluripotency are
regulated by distinct classes of TEs. We will test the hypothesis that RNA derived from one family of TEs acts
in cis as a long non-coding RNA to bind specific sites in the chromatin and promote pluripotency in part by
repressing another family of TEs. Elements of this second family of TEs, in turn, act as promoters for genes
that drive expression of the totipotency program. In Aim 1, we will dissect the antagonistic role of specific TEs
in mouse embryonic stem cells; in Aim 2, we will use cutting-edge technology to dissect the molecular
mechanism of action of a critical family of TEs in embryonic stem cells; in Aim 3, we will define the molecular
role of this TE in early mouse development. This proposal is anticipated to cast pre-implantation development
in an entirely new light, uncovering specific TEs as key mediators of the totipotency-to-pluripotency transition
and deciphering their mechanism of action. This knowledge is expected to have important implications for
understanding and treating infertility, and for using pluripotent stem cells as a platform for studying and treating
degenerative diseases.

## Key facts

- **NIH application ID:** 9878119
- **Project number:** 5R01GM123556-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** MICHAEL T MCMANUS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $388,325
- **Award type:** 5
- **Project period:** 2017-05-19 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9878119

## Citation

> US National Institutes of Health, RePORTER application 9878119, Regulation of developmental potency by the transposon LINE1 (5R01GM123556-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9878119. Licensed CC0.

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