Biology subjects

Emmons-Bell, M.

Publications and source records attributed to Emmons-Bell, M..

2 recordsLinked to original sources

bioRxiv2024

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 processes remains unclear. Here we show that polyamine levels decrease during differentiation and that inhibiting polyamine synthesis leads to a differentiated-like cell state. Polyamines are enriched in the nucleus, where their loss drives changes in chromatin accessibility and histone post-translational modifications. Polyamines interact electrostatically with DNA on the nucleosome core, freeing histone tails to conformations accessible to chromatin-modifying enzymes. Consistent with their role in increasing histone-tail accessibility, polyamines are able to replace MYCs role in reprogramming to pluripotency. These data reveal a mechanism by which an abundant metabolite influences chromatin structure and function in a direct but sequence independent manner, facilitating chromatin remodeling during reprogramming and limiting it during fate commitment.

cell biology↗

bioRxiv2020

Membrane potential regulates Hedgehog signaling and compartment boundary maintenance in the Drosophila wing disc

The Drosophila wing imaginal disc is composed of two lineage-restricted populations of cells separated by a smooth boundary. Hedgehog (Hh) from posterior cells activates a signaling pathway in anterior cells near the boundary which is necessary for boundary maintenance. Here, we show that membrane potential is patterned in the wing disc. Anterior cells near the boundary, where Hh signaling is most active, are more depolarized than posterior cells across the boundary. Elevated expression of the ENaC channel Ripped Pocket (Rpk), observed in these anterior cells, requires Hh. Antagonizing Rpk reduces depolarization and disrupts the compartment boundary. Using genetic and optogenetic manipulations, we show that membrane depolarization promotes membrane localization of Smoothened and augments Hh signaling. Thus, membrane depolarization and Hh-dependent signaling mutually reinforce each other in this region. Finally, clones of depolarized cells survive preferentially in the anterior compartment and clones of hyperpolarized cells survive preferentially in the posterior compartment.

developmental biology↗