Alternative polyadenylation (APA) modulates gene expression by altering 3′ untranslated region (3′UTR) length. Although 3′UTR lengthening typically accompanies cell differentiation, we unexpectedly ob...

Bone fracture healing remains a significant challenge in orthopedics, as injury-responsive skeletal stem cell (SSC) populations and the regulatory mechanisms governing SSC activation during nonunion fracture repair remain poorly delineated. This study identifies zinc finger transcription factor basonuclin-2 (BNC2) as a skeletal fracture repair control factor in periosteal stem cells. BNC2 marks quiescent periosteal cells during homeostasis and is significantly upregulated upon injury in mice, driving endochondral ossification post-fracture via clonal expansion. Moreover, knockout of Bnc2 in Prx1-cre+ cells (not Ocn-cre+ osteoblasts or LepR-creER+ BMSCs) resulted in impaired fracture healing, suppressing SSC proliferation. Mechanistically, ATAC-seq revealed that BNC2 deletion reduced chromatin accessibility at promoter regions of proliferation genes, hindering transcriptional activation. Additionally, BNC2 regulates histone H3 acetylation by interacting with the NuRD complex. Pharmacologically inhibition of HDAC1/2 activity partially ameliorated the fracture repair defects observed in Prx1-cre; Bnc2f/f mice. Collectively, we identified BNC2+ cells as a rapidly expanding periosteal cell population inducing endochondral ossification niches during repair, providing potential therapeutic strategies for nonunion fractures.

Data detectives see validation in deal with U.S. government that penalizes Dana-Farber Cancer Institute for misrepresenting data in NIH grant applications

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...

Fat mass loss is a severe complication in cancer-associated cachexia, but its underlying mechanisms remain unclear. This study identifies the tumor-secreted chaperone clusterin (CLU) as a driver of wh...

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characte...

Small noncoding RNAs (sncRNAs) are subject to 3’-end trimming and tailing activities that impact maturation versus degradation decisions during biogenesis. To investigate the dynamics of human sncRNA ...

The subcellular localization of many mRNAs to neuronal projections allows neurons to efficiently and rapidly react to spatially restricted external cues. However, for most of these RNAs, the mechanism...

The Golgi apparatus is the central hub of secretory and endosomal pathways in a eukaryotic cell. Despite having a conserved basic organization, the Golgi varies greatly in structure and operation mode...

Proximity labeling has emerged as a powerful approach for identifying protein–protein interaction networks within living systems, particularly those involving weak or transient associations. Here, we ...

Somatic hypermutation (SHM) in variable regions of immunoglobulin genes by activation-induced deaminase (AID) is essential for the maturation of protective antibodies against pathogen and vaccine anti...

Microbial translation arrest peptides monitor intracellular environments and feedback-regulate downstream gene expression. Previous studies have identified a class of bacterial arrest peptides with C-...

Following cell entry, HIV-1 capsids enter the nucleus by passage through nuclear pores and reach nuclear speckles with subsequent uncoating of the reverse-transcribed genome and its integration into s...