Biology subjects

Hulo, N.

Publications and source records attributed to Hulo, N..

2 recordsLinked to original sources

bioRxiv2023

ProA and ProB repeat sequences shape genome organization, and enhancers open domains

Genome organization is partially conserved across cell types, yet its DNA-encoded determinants remain incompletely understood. Here we define ProA and ProB repeat sequences (RepSeqs) as two classes of cis-elements that promote A/euchromatin or B/heterochromatin compartment identity. We show that relative ProA/ProB density predicts Hi-C compartment profiles, indicating that compartmental propensity is largely encoded in sequence composition, and point to specific chromatin-based mechanisms underlying these effects. ProA RepSeqs are predominantly Alu elements, whereas ProB RepSeqs comprise young LINE-1s, selected ERVs, AT-rich microsatellites, and satellite repeats. RepSeqs of more indefinite character, including transcriptional enhancers, can switch between ProA and ProB functions to open or close chromatin domains in a context-dependent manner. In cancer, CpG methylation loss disproportionately impacts ProB RepSeqs, weakening the B compartment and thereby contributing to genome unfolding and cancer cell plasticity.

genetics↗

bioRxiv2023

Hsf1 and the molecular chaperone Hsp90 support a "rewiring stress response" leading to an adaptive cell size increase in chronic stress

Cells are exposed to a wide variety of internal and external stresses. Whereas many studies have focused on cellular responses to acute and severe stresses, little is known about how cellular systems adapt to sublethal chronic stresses. Using mammalian cells in culture, we discovered that they adapt to chronic mild stresses of up to two weeks, notably proteotoxic stresses such as heat, by increasing their size and translation, thereby scaling the amount of total protein. These adaptations render them more resilient to persistent and subsequent stresses. We demonstrate that Hsf1, well known for its role in acute stress responses, is required for the cell size increase, and that the molecular chaperone Hsp90 is essential for coupling the cell size increase to augmented translation. We term this translational reprogramming the "rewiring stress response", and propose that this protective process of chronic stress adaptation contributes to the increase in size as cells get older, and that its failure promotes aging.

cell biology↗