Polyamines regulate cell fate by altering the activity of histone-modifying enzymes

Polyamines are polycationic alkyl-amines abundant in proliferating stem and cancer cells. How these metabolites influence numerous cellular functions remains unclear. Here we show that polyamine levels decrease during differentiation and that inhibiting polyamine synthesis leads to a differentiated-...

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Published inbioRxiv
Main Authors Emmons-Bell, Maya, Forsyth, Grace, Sundquist, Abby, Oldeman, Sylvie, Gardikioti, Angeliki, de Souza, Roshni, Coene, Jonathan, Kamel, Maryam H, Ayyapan, Shine, Fuchs, Harrison A, Verhelst, Steven, Smeeton, Joanna, Musselman, Catherine A, Schvartzman, Juan-Manuel
Format Journal Article
LanguageEnglish
Published United States 02.07.2024
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Summary:Polyamines are polycationic alkyl-amines abundant in proliferating stem and cancer cells. How these metabolites influence numerous cellular functions remains unclear. Here we show that polyamine levels decrease during differentiation and that inhibiting polyamine synthesis leads to a differentiated-like cell state. Polyamines concentrate in the nucleus and are further enriched in the nucleoli of cells in culture and . Loss of polyamines drives changes in chromatin accessibility that correlate with altered histone post-translational modifications. Polyamines interact electrostatically with DNA on the nucleosome core, stabilizing histone tails in conformations accessible to modifying enzymes. These data reveal a mechanism by which an abundant metabolite influences chromatin structure and function in a non-sequence specific manner, facilitating chromatin remodeling during reprogramming and limiting it during fate commitment.
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ISSN:2692-8205
2692-8205
DOI:10.1101/2024.07.02.600738