Abstract
Mammalian erythropoiesis involves chromatin condensation that is initiated in the early stage of terminal differentiation. The mechanisms of chromatin condensation during erythropoiesis are unclear. Here, we show that the mouse erythroblast forms large, transient, and recurrent nuclear openings that coincide with the condensation process. The opening lacks nuclear lamina, nuclear pore complexes, and nuclear membrane, but it is distinct from nuclear envelope changes that occur during apoptosis and mitosis. A fraction of the major histones are released from the nuclear opening and degraded in the cytoplasm. We demonstrate that caspase-3 is required for the nuclear opening formation throughout terminal erythropoiesis. Loss of caspase-3 or ectopic expression of a caspase-3 non-cleavable lamin B mutant blocks nuclear opening formation, histone release, chromatin condensation, and terminal erythroid differentiation. We conclude that caspase-3-mediated nuclear opening formation accompanied by histone release from the opening is a critical step toward chromatin condensation during erythropoiesis in mice.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 498-510 |
| Number of pages | 13 |
| Journal | Developmental Cell |
| Volume | 36 |
| Issue number | 5 |
| DOIs | |
| State | Published - Mar 7 2016 |
Funding
We thank J.D. Crispino, R. Burgess, and T. Misteli for critical reading of the paper; W.A. Muller, Y. Chen, R.D. Goldman, T. Shimi, J. Palis, and D. Fang for helpful discussion; L. Reynolds, Jr. and J. Wu for the help with electron microscopy; J.D. Crispino for kindly providing the G1ER cell line; and C. Arvanitis for the help with confocal microscopy. This work made use of the EPIC facility (NUANCE Center-Northwestern University), which has received support from the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the CryoCluster equipment, which has received support from the MRI program (NSF DMR-1229693); the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This work was supported by American Society for Hematology Scholar Award , NIH pathway to independence award ( R00HL102154 ), Chicago Biomedical Consortium Catalyst Award (C059), and National Cancer Institute grant ( U54CA143869 ) to P.J. We thank J.D. Crispino, R. Burgess, and T. Misteli for critical reading of the paper; W.A. Muller, Y. Chen, R.D. Goldman, T. Shimi, J. Palis, and D. Fang for helpful discussion; L. Reynolds, Jr. and J. Wu for the help with electron microscopy; J.D. Crispino for kindly providing the G1ER cell line; and C. Arvanitis for the help with confocal microscopy. This work made use of the EPIC facility (NUANCE Center-Northwestern University), which has received support from the MRSEC program (NSF DMR-1121262) at the Materials Research Center; the CryoCluster equipment, which has received support from the MRI program (NSF DMR-1229693); the International Institute for Nanotechnology (IIN); and the State of Illinois, through the IIN. Imaging work was performed at the Northwestern University Center for Advanced Microscopy generously supported by NCI CCSG P30 CA060553 awarded to the Robert H. Lurie Comprehensive Cancer Center. This work was supported by American Society for Hematology Scholar Award, NIH pathway to independence award (R00HL102154), Chicago Biomedical Consortium Catalyst Award (C059), and National Cancer Institute grant (U54CA143869) to P.J.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology
- Molecular Biology
- Cell Biology
- Developmental Biology