Integrative PTEN Enhancer Discovery Reveals a New Model of Enhancer Organization
Cerda-Smith, C.; Hutchinson, H. M.; Liu, A.; Goel, V. Y.; Sept, C.; Kim, H.; Casani-Galdon, S.; Burkman, K. G.; Bassil, C. F.; Hansen, A. S.; Aryee, M. J.; Johnstone, S. E.; Eyler, C. E.; Wood, K. C.
Show abstract
Enhancers possess both structural elements mediating promoter looping and functional elements mediating gene expression. Traditional models of enhancer-mediated gene regulation imply genomic overlap or immediate adjacency of these elements. We test this model by combining densely-tiled CRISPRa screening with nucleosome-resolution Region Capture Micro-C topology analysis. Using this integrated approach, we comprehensively define the cis-regulatory landscape for the tumor suppressor PTEN, identifying and validating 10 distinct enhancers and defining their 3D spatial organization. Unexpectedly, we identify several long-range functional enhancers whose promoter proximity is facilitated by chromatin loop anchors several kilobases away, and demonstrate that accounting for this spatial separation improves the computational prediction of validated enhancers. Thus, we propose a new model of enhancer organization incorporating spatial separation of essential functional and structural components.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals 97%
- Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells 96%
- Simultaneous epigenomic profiling and regulatory activity measurement using e2MPRA 96%
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- High throughput PRIME editing screens identify functional DNA variants in the human genome 97%
- Systematic Dissection of Sequence Features Affecting the Binding Specificity of a Pioneer Factor Reveals Binding Synergy Between FOXA1 and AP-1 96%
- Widespread variation in molecular interactions and regulatory properties among transcription factor isoforms 96%
"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.