# Epigenetic regulation of transcriptional programming

> **NIH NIH R35** · BRIGHAM AND WOMEN'S HOSPITAL · 2022 · $717,602

## Abstract

PROJECT SUMMARY
The genomes of higher organisms are highly annotated by specific chromosomal proteins and
histone modifications along active genes, regulatory elements, or silent regions. This annotation is
critical for proper cell type specification, and an ongoing challenge is to decipher the rules that
establish and maintain chromatin organization. My laboratory focuses on analysis of chromatin
regulatory complexes, based on their central importance in development and disease, the intriguing
hypotheses raised by our recent studies, and our ability to use new approaches to probe chromatin
protein interactions with precision. Historically, we have made significant contributions to
understanding the targeting and spreading of chromatin domains, and currently we are probing the
ability of chromatin factors to poise genes for key regulatory decisions that specify cell type. Our
current studies focus on the Polycomb group (PcG) proteins, and due to the high conservation of this
key regulatory system we move between fly embryos and human embryonic stem cells with ease. We
are developing a model in which key regulatory genes are universally ‘poised’ early in development
via occupancy of composite protein complexes of Polycomb Repressive Complex 1 (PRC1) and
classical co-activators. These ‘bivalent’ protein complexes may resolve into full activation or
repression, depending on the cell type-specific expression, binding, and function of transcription
factors. We speculate that transcription factors may bind relatively promiscuously, but still execute
precise regulatory decisions, when they influence the local acetylation/deacetylation state at these
predetermined sites. Our speculative model is based on strong proteomic evidence that PRC1
strongly interacts with classic co-activators, dBRD4 and dMOZ/MORF, captured on chromatin during
embryogenesis in Drosophila, and by analogous co-occupancy of CBX7, RING2 (subunits of PRC1),
and BRD1 (a subunit of MOZ/MORF) in human embryonic stem cells. We believe that we are on the
cusp of understanding chromatin transitions and transcriptional programming at a mechanistic level.
These studies also synergize with our molecular dissection of aberrant chromatin complexes that
drive human cancers.

## Key facts

- **NIH application ID:** 10398124
- **Project number:** 5R35GM126944-05
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Mitzi I Kuroda
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $717,602
- **Award type:** 5
- **Project period:** 2018-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10398124

## Citation

> US National Institutes of Health, RePORTER application 10398124, Epigenetic regulation of transcriptional programming (5R35GM126944-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10398124. Licensed CC0.

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