RT Journal Article
SR Electronic
T1 Hierarchical chromatin regulation during blood formation uncovered by single-cell sortChIC
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.04.26.440606
DO 10.1101/2021.04.26.440606
A1 Zeller, Peter
A1 Yeung, Jake
A1 de Barbanson, Buys Anton
A1 Gaza, Helena Viñas
A1 Florescu, Maria
A1 van Oudenaarden, Alexander
YR 2021
UL http://biorxiv.org/content/early/2021/04/26/2021.04.26.440606.abstract
AB Post-translational histone modifications modulate chromatin packing to regulate gene expression. How chromatin states, at euchromatic and heterochromatic regions, underlie cell fate decisions in single cells is relatively unexplored. We develop sort assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in hematopoietic stem and progenitor cells (HSPCs), and mature blood cells in the mouse bone marrow. During differentiation, HSPCs acquire distinct active chromatin states that depend on the specific cell fate, mediated by cell type-specifying transcription factors. By contrast, most regions that gain or lose repressive marks during differentiation do so independent of cell fate. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin-repressed states. This suggests hierarchical chromatin regulation during hematopoiesis: heterochromatin dynamics define differentiation trajectories and lineages, while euchromatin dynamics establish cell types within lineages.Competing Interest StatementThe authors have declared no competing interest.