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

Award Number: R15NS133909
ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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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.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2024 ( Subtotal = $456,000 )
2024	2024	KENT STATE UNIVERSITY	1500 HORNING RD	KENT	OH	44242	PORTAGE	USA	Extramural Research Programs in the Neurosciences and Neurological Disorders	000	1	9/3/2024	NEW	$456,000
														Subtotal = $456,000

Grand Total All Awards = $456,000

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

Award Number: R15NS133909

ORGANIZATION: NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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