Chromatin condensation in terminally differentiating mouse erythroblasts does not involve special architectural proteins but depends on histone deacetylation

Journal Article · Thu Aug 21 04:00:00 EDT 2008 · Chromosome Research

OSTI ID:966051

Popova, Evgenya Y; Krauss, Sharon Wald; Short, Sarah A; Lee, Gloria; Villalobos, Jonathan; Etzell, Joan; Koury, Mark J; Ney, Paul A; Chasis, Joel Anne; Grigoryev, Sergei A

Terminal erythroid differentiation in vertebrates is characterized by progressive heterochromatin formation, 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 virus-infected murine spleen erythroblasts that undergo terminal differentiation in vitro. Chromatin isolated from early and late stage 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 H3(K9) dimethylation markedly increased while histone H4(K12) 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 virus-infected 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 developmentally-regulated architectural proteins in nucleated blood cells.

• Research Organization: Ernest Orlando Lawrence Berkeley National Laboratory, Berkeley, CA (US)
• Sponsoring Organization: Life Sciences Division
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 966051
• Report Number(s): LBNL-2237E
• Journal Information: Chromosome Research, Journal Name: Chromosome Research Vol. 17; ISSN 0967-3849
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
ACETYLATION
BLOOD CELLS
BONE MARROW CELLS
CHROMATIN
ERYTHROPOIESIS
EXTRUSION
HETEROCHROMATIN
HISTONES
IN VITRO
MAMMALS
METHYLATION
NUCLEOSOMES
PROTEINS
SPLEEN
VERTEBRATES