chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation and chromatin condensation and in mammals culminates in nuclear extrusion to date although mechanisms regulating avian erythroid chromatin condensation have been identified little is known regarding this process during mammalian erythropoiesis to elucidate the molecular basis for mammalian erythroblast chromatin condensation we used friend virusinfected murine spleen erythroblasts that undergo terminal differentiation in vitro chromatin isolated from early and latestage erythroblasts had similar levels of linker and core histones only a slight difference in nucleosome repeats and no significant accumulation of known developmentally regulated architectural chromatin proteins however histone h3k9 dimethylation markedly increased while histone h4k12 acetylation dramatically decreased and became segregated from the histone methylation as chromatin condensed one histone deacetylase hdac5 was significantly upregulated during the terminal stages of friend virusinfected erythroblast differentiation treatment with histone deacetylase inhibitor trichostatin a blocked both chromatin condensation and nuclear extrusion based on our data we propose a model for a unique mechanism in which extensive histone deacetylation at pericentromeric heterochromatin mediates heterochromatin condensation in vertebrate erythroblasts that would otherwise be mediated by developmentallyregulated architectural proteins in nucleated blood cells