# Cell-cycle dependent gene transcription through activation of B-Myb

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $38,374

## Abstract

PROJECT SUMMARY
The cell cycle is a carefully controlled cellular process that maintains the integrity of organismal growth.
Deregulation of the cell cycle leads to cell death or irregular cell growth which is a common trait seen in cancer.
One hallmark of the cell cycle is the periodic expression of cell-cycle genes. Timing of cell cycle-dependent
gene expression is regulated by multiple transcription factors. Recently, MuvB complexes had been identified
to regulate the expression of several hundred cell-cycle dependent gene expression. In non-proliferating cells,
the MuvB core complex represses transcription by binding to E2F4-p130. Upon entering the cell cycle, MuvB
dissociates from E2F4-p130 and binds to B-Myb in S phase to activate mitotic genes. B-Myb is expressed in
all proliferating cells and loss of function leads to reduced mitotic gene expression and to early embryonic
lethality in mice. Overexpression of B-Myb is implicated in breast, lung and colon cancer. ChIP data of B-Myb
show that many mitotic genes are direct targets of the B-Myb-MuvB (MMB) complex, however, canonical Myb
binding site (MBS) are not commonly found in cell-cycle promoters. Even if B-Myb was originally described as
a sequence- specific transcription factor interacting with MBS, several lines of evidence imply that B-Myb is
recruited to mitotic genes through MuvB binding to CHR promoter elements. In this case, B-Myb may rather
contact the DNA in a non-sequence-specific manner. By fluorescence polarization and electromobility shift
assays I have determined that B-Myb binds to reconstituted Widom nucleosomes through its N-terminal DNA
binding domain (DBD). Thus, my working hypothesis is that B-Myb binds to nucleosomes through its DNA
binding domain to stabilize MuvB at cell-cycle gene promoters to recruit the co-activator p300/CBP and this
activity is regulated through multi-site phosphorylation. In aim 1, I will analyze the association modes of B-Myb-
nucleosome complex by solving the high-resolution cryo-EM structure and how it regulates MMB occupancy at
cell-cycle promoters. In aim 2, I will determine how phosphorylation regulates its auto-inhibitory state to bind
with co-activator p300/CBP. Completion of these aims will enhance our knowledge on how B-Myb can activate
cell-cycle dependent genes.

## Key facts

- **NIH application ID:** 10313815
- **Project number:** 1F31CA254090-01A1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Tilini Wijeratne
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $38,374
- **Award type:** 1
- **Project period:** 2021-08-01 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10313815

## Citation

> US National Institutes of Health, RePORTER application 10313815, Cell-cycle dependent gene transcription through activation of B-Myb (1F31CA254090-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10313815. Licensed CC0.

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