# The hemoglobin beta subunit regulates chromatin and transcription to adapt to metabolic demands

> **NIH NIH R15** · KENT STATE UNIVERSITY · 2024 · $456,000

## Abstract

Abstract
 Several studies have reported that hemoglobin is expressed in neurons in the rodent and human
brain, however the function of hemoglobin in these cells hasn't been clearly defined. The long term goal
of this research is to better understand why hemoglobin is expressed in cells other than red blood cells.
The hemoglobin  and  subunits (Hba and Hbb) are expressed in neurons in the brain, but only Hbb is
localized to the nucleus. In this proposal our objective is to understand why Hbb is expressed in the
nucleus and to uncover mechanisms involved in Hbb signaling. We have found that Hbb interacts with
chromatin where it inhibits the activity of the KDM5B histone demethylase by sequestering oxygen
required for KDM5B activity. Hbb mediated inhibition of KDM5B results in increased levels of H3K4me3,
a histone mark that activates transcription. The aims of this proposal will test the hypothesis: that
Hbb regulates chromatin and transcription in the brain to adapt to metabolic demands. In aim 1: ChIP-
seq will be employed to find out where Hbb is bound to chromatin and which genes are regulated by Hbb
signaling in primary neuronal cultures. In aim 2: Effects of Hbb on bioenergetics will be assessed with
Seahorse respirometry. Aim 3: will test the role of exercise on regulation of Hbb signaling pathways and
energy metabolism in the brain. The proposed study will increase the understanding of mechanisms
involved in regulating the chromatin landscape and gene expression related to balancing energy
metabolism needs.

## Key facts

- **NIH application ID:** 10974639
- **Project number:** 1R15NS133909-01A1
- **Recipient organization:** KENT STATE UNIVERSITY
- **Principal Investigator:** Jennifer McDonough
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $456,000
- **Award type:** 1
- **Project period:** 2024-09-04 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10974639

## Citation

> US National Institutes of Health, RePORTER application 10974639, The hemoglobin beta subunit regulates chromatin and transcription to adapt to metabolic demands (1R15NS133909-01A1). Retrieved via AI Analytics 2026-07-27 from https://api.ai-analytics.org/grant/nih/10974639. Licensed CC0.

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