Dynamic changes in Lamin B1 and heterochromatin coincide with chromatin condensation during human erythropoiesis

Chromatin condensation, accompanied by pronounced nuclear shrinkage, is a pivotal step in terminal erythroid differentiation and is essential for enucleation. However, the precise timing and molecular mechanisms initiating this process remain poorly understood, particularly as global transcriptional repression occurs only at the orthochromatic erythroblast stage.

Here we perform a comprehensive analysis of three-dimensional chromatin architecture dynamics during erythropoiesis using integrative epigenomic and imaging approaches. We demonstrate that chromatin condensation begins earlier than previously recognized, initiating at the late basophilic erythroblast stage. Mechanistically, these intergenic regions were tethered to the nuclear lamina (predominantly heterochromatic) and enriched in H3K9me3, which drive large-scale chromatin compaction. Furthermore, we find that the redistribution of H3K9me3 and dynamic remodeling of Lamin B1 are critical for this structural transition, directly impacting erythroid maturation.

These findings reveal a previously unrecognized regulatory axis linking H3K9me3 and chromatin-lamina interactions, providing novel insights into the spatial and temporal control of chromatin organization during erythroid development.