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Characterizing Histone Post-translational Modification Alterations in Yeast Neurodegenerative Proteinopathy Models
Published on: March 24, 2019
Neuronal expression of bromodomain proteins alters neuronal health and peripheral protein homeostasis to promote
Naibedya Dutta1, Daniel Hicks1, Edgar Esparza2
1Leonard Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA.
Abstract:
Longevity and stress resilience require precise coordination of gene expression programs across tissues. Here, we demonstrate that overexpression of the chromatin reader bet-1 specifically in neurons of Caenorhabditis elegans promotes organismal longevity and stress resistance via cell-nonautonomous signaling. Neuronal bet-1 elicits a neurotransmitter-dependent signal that activates the conserved stress-responsive transcription factor HSF-1 in the intestine, enhancing proteostasis, oxidative stress resistance, metabolic remodeling, and immune defense. Life span extension by neuronal bet-1 requires both hsf-1 and daf-16 in neurons but only requires hsf-1 in peripheral tissues. Using bulk RNA sequencing, we reveal distinct prolongevity pathways that include enhanced heat-shock response, proteostasis, increased actin stability, and resistance to pathogens, which likely together coordinate the prolongevity effects of neuronal bet-1 Our findings establish BET-1 as a potent nonautonomous regulator of aging and stress response, highlighting chromatin readers as upstream modulators of intertissue signaling and systemic resilience.
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