Fig. 8: Models incorporating Evf2 RNA direct binding, RNP recruitment, enhancer guidance, transcriptional regulation, and intra- and inter-chromosomal looping interactions. | Nature Communications

Fig. 8: Models incorporating Evf2 RNA direct binding, RNP recruitment, enhancer guidance, transcriptional regulation, and intra- and inter-chromosomal looping interactions.

From: Single-cell transcriptomics of ventral forebrain progenitors identifies Evf2 enhancer lncRNA-enhancer gene guidance through direct RNA binding and RNP recruitment domains

Fig. 8: Models incorporating Evf2 RNA direct binding, RNP recruitment, enhancer guidance, transcriptional regulation, and intra- and inter-chromosomal looping interactions.The alternative text for this image may have been generated using AI.

A–C Models of multi-level Evf2 regulation on mouse chr6 resulting from RBS stabilized divisions, EGGs and RNP recruitment. A Relationships between RBSs (purple ovals), DNA sequence identity, G-quadruplex (GQ), RNP recruitment, EGG-GBs corresponding to scRNAseq transcriptional targets (colored loops, top), short-range activation and long-range repression domains, aligned with all EGGs (Evf2 regulated +/- Dlx5/6UCE sites). B 1. Evf2 (blue arrow) expressed from the Dlx5/6UCE enhancer E, recruits RNPs/PPCs (yellow oval), to E, 2. Evf1/2 binds at chr6-RBS 1−3, facilitating DNA looping (purple oval/hairpin), recruiting RNPs, 3. Multi-modal EGG−3D changes (black arrows), 4–5. RNP recruitment and gene transcription (repression (red), activation (green). C RBSs spaced at >105 bp apart define 5 chromosomal domains on mo-chr6. The black arrow points to the cluster of RBS 1-3. In wildtype (WT) E13.5GE nuclei, the majority of inter-chr loops on chr6 (29/35) are located in RCD 1, proximal to Evf2/Dlx5/6UCE (blue square), overlapping with Evf2-positively regulated DLX ((+), green) enrichment. In wildtype E13.5GE nuclei, RCD 2 is enriched for intra-chromosomal looping, and both positive and negative regulation of RNP binding. RCDs define boundaries for TF motif enrichment at Evf2-regulated SMARCC2 and NONO sites. D i. Inter-chr interactions with chr6 proximal end (P) detected by HiC. RNP recruitment at hotspots near interaction sites, indicated by arrows to yellow ovals, and transcriptional effects on genes located on chr6 and on interacting chromosomes are indicated by the black boxes. ii–iii. Models of intra-chr super-looping through simultaneously paired inter-chr looping. ii. The blue ovals indicating pairs of chr6-chr4 HiC interaction sites. The distance between HiC sites on chr4 is 38.4 M, but on chr6 is 108 Mb. iii. The blue ovals indicate pairs of chr6-chr8 HiC interaction sites. E Potential RCD-defined 3-D stabilized looping (1–4) of enhancer-gene groups, with effects of the enhancer on looped domains indicated by arrows. i. sequential, ii. Nested loops, iii. Clover, iv. In the absence of Evf2, relaxed looping increases enhancer-gene targets within domains.

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