# Developmental gene poising by Oct transcription factors

> **NIH NIH R01** · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2021 · $305,000

## Abstract

PROJECT SUMMARY:
Oct4 is a master transcriptional regulator of pluripotency. Intriguingly, embryonic stem cells (ESCs) and
induced pluripotent stem cells (iPSCs) co-express Oct4 together with two paralogs, Oct1 and Oct6. These
proteins bind the same sequences in vitro and many of the same genes in vivo. Their functions in pre-
implantation embryos and ESCs, and immediately following differentiation, are unknown. Though critical early
developmental fate decisions are made as ESCs first lose pluripotency and Oct4 is lost, how this process
works at a molecular level remains a black box. For example, developmentally poised Oct4 targets can be
induced many days after loss of Oct4 itself, raising the question of how poising is maintained. This proposal
focuses on Oct1/Oct6/Oct4 collaboration in pluripotent cells and early during differentiation. We previously
showed that Oct1 either represses gene transcription, by associating with NuRD, or maintains silent genes in a
configuration that allows for later expression, by associating with Jmjd1a/KDM3A to decrease local histone
H3K9 methylation. More recently we showed that Oct1 is dispensable in undifferentiated ESCs, but following
differentiation is required both to induce developmental-specific genes, and to suppress genes specific for
alternative developmental lineages. As a consequence, Oct1 deficient ESCs appear normal but show severe
defects upon differentiation. Oct1 does not occupy these targets in ESCs, presumably due to competition from
the more abundant Oct4 protein. Instead, Oct1 occupies these genes as ESCs differentiate and Oct4 is lost.
We propose a “handoff” model whereby silent but poised genes are occupied by Oct1, and possibly Oct6, to
maintain proper developmental gene expression. We will test this model by identifying common and unique
Oct1/Oct4/Oct6 target sites genome-wide in differentiating ESCs, determining whether handoff of cofactors
accompanies Oct4 replacement by Oct1 in differentiating cells, and studying Oct1-mediated repression of
lineage-inappropriate genes, which are ectopically expressed upon differentiation of Oct1 deficient ESCs.
Aim 1: Test the validity of the handoff model.
Aim 2: Define the cofactors used by Oct1 and Oct4 at developmentally inducible targets in pluripotent cells and
immediately after differentiation.
Aim 3: Determine the mechanism by which Oct1 represses lineage-inappropriate genes.

## Key facts

- **NIH application ID:** 10111526
- **Project number:** 5R01GM122778-04
- **Recipient organization:** UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
- **Principal Investigator:** DEAN TANTIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $305,000
- **Award type:** 5
- **Project period:** 2018-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111526

## Citation

> US National Institutes of Health, RePORTER application 10111526, Developmental gene poising by Oct transcription factors (5R01GM122778-04). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10111526. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*