# The Role of Baf45a in Bone Formation

> **NIH NIH F30** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $50,480

## Abstract

Bone loss is a worldwide problem resulting in increased risk of fracture and tooth loss27. Osteoblasts are
responsible for bone synthesis; therefore, treatments promoting osteoblast differentiation and/or activity would
result in increased bone formation28. The regulation of DNA accessibility is a key mechanism controlling gene
expression and cellular differentiation. BAF (BRG1 Associated Factor) mediated Chromatin remodeling
increases DNA accessibility by sliding or ejecting nucleosomes1,2,14. This process can occur in a cell type or
stage specific manner based on the composition of the BAF complex4. In many tissue types, a unique
combination of BAF subunits has been identified to be responsible for the maintenance or differentiation of that
cell type4,5,6,7. To date, an osteoblast specific BAF chromatin remodeling complex has yet to be identified. It has
been recently found in our studies that BAF45A, a potential member of the BAF complex, plays an essential
role in osteoblast differentiation and function. The purpose of this study is to address our central hypothesis
that that BAF45A is critical to remodel and activate chromatin at osteoblast specific genes promoting
the synthesis and maintenance of bone. In order to address this hypothesis the study has been divided into
two specific aims. 1) Define the phenotype of BAF45A osteoblast-specific knockout mice: To accomplish
this aim, we have developed an osteoblast-specific knockout of Baf45a. This is done by crossing a Baf45a
floxed allele mouse with an osteoblast specific osteocalcin-Cre mouse. The physical phenotype of this mouse
will be analyzed by whole skeletal staining, microCT, histology/histomorphometry, double calcein labeling, and
a three-point bend test. The molecular properties will be assessed using real time PCR for osteoblastic gene
expression analysis, and chromatin-immunoprecipitation in order to understand the corresponding chromatin
state at osteoblast specific genes. 2) Identify osteoblast differentiation stage-specific BAF complex
composition: To uncover the composition of the osteoblast specific BAF complex, a biotin proximity ligation
technique will be employed. A promiscuous biotin ligase will be linked with BAF45A and proteins in close
proximity will be biotinylated, pulled-down, and identified by mass spectrometry. This will be confirmed by co-
immunoprecipitation. Understanding the physiological role and molecular mechanism of Baf45a as well as the
composition of BAF in osteoblasts will reveal novel insights into osteoblast development and function. This
may ultimately result in the development of treatments targeted to increase osteoblast differentiation and
activity to increase bone mass.

## Key facts

- **NIH application ID:** 9906052
- **Project number:** 5F30DE027280-03
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Tanner Cole Godfrey
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,480
- **Award type:** 5
- **Project period:** 2018-06-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9906052

## Citation

> US National Institutes of Health, RePORTER application 9906052, The Role of Baf45a in Bone Formation (5F30DE027280-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9906052. Licensed CC0.

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