A collaborative effort between Mount Sinai and Memorial Sloan Kettering Cancer Center has shed valuable light on how monoamine neurotransmitters such as serotonin, dopamine, and now histamine help regulate brain physiology and behavior through chemical bonding of these monoamines to histone proteins, the core DNA-packaging proteins of our cells.
The Mount Sinai Hospital / Mount Sinai School of Medicine Jan 9 2025
"This groundbreaking mechanism reveals, for the first time, how circadian events that stimulate neurotransmitter signaling in the brain can exert dynamic effects on neurons by directly altering DNA structure," adds Yael David, PhD, a chemical biologist who leads The Yael David Lab at Memorial Sloan Kettering Cancer Center and co-lead author of the study.
"The idea originated from a simple observation of the chemical intermediates formed by TG2 with its co-factor, revealing a new dynamic," says study first author, Qingfei Zheng, PhD, a previous postdoctoral fellow in the Yael David Lab, who is now a faculty member at Purdue University. Based on this novel mechanism of action, the team speculated that intracellular fluctuations in monoamine concentrations can lead to their selective utilization by TG2, which could then trigger new histone modifications. Indeed, investigators identified histaminylation as a new modification of histones and showed that it, along with the allied process known as H3 serotonylation, plays a critical role in regulating circadian rhythms in the mouse brain, along with circadian behavior.
Gene Gene Expression Bipolar Disorder Cancer Circadian Rhythm Depression DNA Dopamine Health Care Histamine Histones Hospital Insomnia Intracellular Medicine Neurodegenerative Disease Neuroscience Physiology Research Serotonin Sleep
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