State-Dependent Regulatory Compression: Chromatin Geometry Gates Information Flow in Hematopoiesis
Quiroz, R. c. N.; Quiroz, E. N.
Show abstract
Geometric constraints in chromatin-transcription space--regions of low occupancy termed "forbidden zones"-- have been interpreted as signatures of regulatory dissociation in progenitor cells. We previously falsified this interpretation: progenitors exhibit higher, not lower, mutual information between chromatin accessibility and transcription. Here we address the consequent question: what organizational principle governs coupling under geometric constraint? Using human bone marrow multiome data (GSE194122; N=13 donors, 69,249 cells), we operationalize the Law of State-Dependent Regulatory Compression (LCR-DE) through three metrics: Gate Occupancy (GO), Coupling Efficiency (CE), and Control Selectivity (CS). Progenitors maintain conserved geometric boundaries (GO: Wilcoxon p=0.94) while exhibiting elevated coupling efficiency (CE: median 0.058 vs 0.019; p=9.77x 10-3). The lower CS in progenitors reflects distributed regulatory redundancy across multilineage programs, not absence of control, while differentiated cells exhibit crystallized, pathway-specific channeling. CE persists after cell cycle residualization (p=0.64), confirming biological rather than proliferative origin. These findings establish regulatory compression--informational channeling through selective pathways under geometric constraint--as an organizational principle of hematopoietic differentiation.
Matching journals
The top 8 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Niche signals regulate continuous transcriptional states in hematopoietic stem cells 93%
- Efficient differentiation of human primordial germ cells through geometric control reveals a key role for NODAL signaling 92%
- Paths and Pathways that Generate Cell-Type Heterogeneity and Developmental Progression in Hematopoiesis 91%
Similar papers in this journal
- Dynamic Runx1 chromatin boundaries affect gene expression in hematopoietic development 93%
- A statistical framework for differential pseudotime analysis with multiple single-cell RNA-seq samples 92%
- A robust model for cell type-specific interindividual variation in single-cell RNA sequencing data 92%
Similar papers in this journal
- Active regulatory elements recruit cohesin to establish cell-specific chromatin domains. 92%
- Pseudotime analysis reveals novel regulatory factors for multigenic onset and monogenic transition of odorant receptor expression 92%
- Integrative network modeling reveals mechanisms underlying T cell exhaustion 91%
Similar papers in this journal
- Binomial models uncover biological variation during feature selection of droplet-based single-cell RNA sequencing 92%
- Transcriptional bursts explain autosomal random monoallelic expression and affect allelic imbalance 92%
- Identifying Reproducible Transcription Regulator Coexpression Patterns with Single Cell Transcriptomics 92%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.