bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/2025.03.20.644273

Protamine sequence determines species-specific nuclear shape and histone retention

Czernik, M.·Palazzese, L.·Winiarczyk, D.·Iuso, D.·Khochbin, S.·Fulka, J.·Fulka, H.·Villafranca, R.·Rielo, J. A.·Sanchez-Rodriguez, A.·Latorre, N.·Agudo-Rios, C.·Roldan, E.·Teves, M. E.·Loi, P.
View original source ↗Export metadata ↓

Abstract

Nuclear shape observed after the forced expression of mouse or human Protamine 1 (PRM1) in fibroblasts led us to propose the hypothesis that PRM1 sequence plays an important role in imposing the overall shape of the protaminized nucleus. Comparison of mouse and human PRM1 sequence pointed to cysteines 15 and 29 as potential critical residues in the mouse PRM1 sequence inducing the characteristic mouse "hooked" nuclear sperm shape. To explore this idea, mice with mutations in PRM1 Cys15 and Cys29 were generated. These mice remained fertile with no significant changes in sperm count or protamine expression levels. However, modifications in sperm head shape were observed. Transmission electron microscopy revealed disrupted chromatin condensation in mutant sperm, with several morphological changes and a remarkable increase in histone retention. Overall, the findings suggest that species-specific PRM1 cysteine residue positions are crucial for nuclear shape determination and histone retention in spermatozoa.

Source connections

Explore related subjects

developmental biologyPreprint

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Czernik, M., Palazzese, L., Winiarczyk, D., Iuso, D., Khochbin, S., Fulka, J., Fulka, H., Villafranca, R., Rielo, J. A., Sanchez-Rodriguez, A., Latorre, N., Agudo-Rios, C., Roldan, E., Teves, M. E., Loi, P.. 2025-03-22. Protamine sequence determines species-specific nuclear shape and histone retention. https://doi.org/10.1101/2025.03.20.644273

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

bioRxiv2026

Alveolar and airway progenitors converge on an epigenetically encoded profibrotic state

During organ regeneration, epithelial transitional states arise from progenitors and instruct the mesenchyme to remodel the extracellular matrix. However, the identity of the progenitors, the mechanisms underlying this transition, and why these states persist in tissue fibrosis often remain elusive. Here, using lineage tracing in mice, we show that the profibrotic KRT5-/KRT17+ state in pulmonary fibrosis arises convergently from alveolar type (AT) 2 and airway secretory cells. AT1 cells generate neither KRT5-/KRT17+ nor AT2 cells. TGF-{beta}/SMAD3 acts through KMT2A and p300 to epigenetically reprogram human AT2 cells into the KRT5-/KRT17+ state. In human pulmonary fibrosis, KRT5-/KRT17+ cells slough off, and transitional cells re-epithelialize the denuded basement membrane. Transcriptionally convergent states arise in injured kidney, skin, and intestine. This work reframes fibrogenesis as the accumulation of a conserved profibrotic transitional state via ongoing turnover, not persistence alone, and nominates the state transition and its epigenetic regulators as therapeutic targets.

developmental biology↗
bioRxiv2026

Dynamic mechanical sorting biases niche occupancy and lineage outcome during development of bilayered glandular epithelia

Tissue compartmentalization into basal and luminal domains is a hallmark of glandular epithelia, yet how fate boundaries are established and stabilized during dynamic morphogenesis remains a major unresolved question. Here, using mouse embryonic explants, organoids, quantitative live imaging and genetic perturbations, we show that basal-luminal compartmentalization is not maintained by fixed boundaries, but through continuous positional corrections. We show that differences in cellular adhesion and actomyosin contractility drive these positional corrections by promoting active cell sorting. We further find that these mechanical differences influence lineage specification by controlling cell positioning rather than directly instructing cell fate. Before commitment, mosaic, but not uniform, perturbation of cell mechanics alters niche occupancy and biases lineage outcome, indicating that relative mechanical properties determine access to fate-instructive niches. Conversely, perturbation of Notch and YAP remodels compartment-specific mechanical properties and cell-positioning dynamics, revealing a reciprocal coupling between lineage state and mechanical sorting. Conservation of this mechanism across four glandular epithelia of distinct origins and functions identifies dynamic mechanical sorting as a general strategy for maintaining robust tissue compartmentalization during the extensive growth and cellular rearrangements of branching morphogenesis.

developmental biology↗
bioRxiv2026

Unbiased lineage tracing across the adipose organ decouples developmental origin from anatomical and transcriptomic identities

The developmental origins of individual adipose depots and whether embryonic lineage dictates adult function remain unresolved. Here, we apply in utero CRISPR-mediated barcoding lineage tracing to construct the first unbiased clonal map of adipose organ development in mice. The developmental hierarchy we uncover challenges several conventions. Remarkably, interscapular brown fat, used as the prototypical brown fat, is the most developmentally isolated brown fat; depots sharing Myf5/Pax3 lineage markers fail to cluster together; mesenteric white fat shares unexpected high clonal ancestry with brown fats despite a radically divergent transcriptome; and subcutaneous white adipose tissues converge transcriptomically despite distant developmental origins. These findings call for a reinterpretation of single-marker lineage tracing data across the adipose organ and propose that adipose depot identity is not solely encoded by embryonic lineage but is substantially shaped by the anatomical niche.

developmental biology↗