ArticleInvestigative ophthalmology & visual science2025
The 3D Genome Structure of a Blcap-Linked Silencer Loop Regulates Terminal Differentiation During Lens Fiber Cell Denucleation.
Article in Investigative ophthalmology & visual science, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
0 citing papers in PubMed.
No citing paper in PubMed yet.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: Lens fiber cells (LFCs) remove their nuclei and organelles during terminal differentiation through a controlled process that resembles, but does not execute, apoptosis. The mechanisms that inhibit apoptotic pathways while permitting nuclear degradation remain unclear. Using Hi-C, CUT&Tag, and RNA-seq, we mapped chromatin and epigenetic changes during the LEC-to-LFC transition. We focused on a distal silencer region (DSR)-mediated chromatin loop near Blcap and its function in repressing apoptosis-related signaling to support proper nuclear clearance and lens transparency. Methods: Hi-C sequencing mapped chromatin architecture in E16.5 mouse LECs and LFCs, focusing on apoptosis-related loci. CUT&Tag profiling for H3K27me3, CTCF, and SMC3, integrated with RNA-seq, identified a novel silencer element and an LFC-specific chromatin loop linking Blcap to the DSR. To assess function, an adeno-associated virus-delivered saCas9 dual-sgRNA system was used to delete loop anchor regions in vivo. Functional effects were validated through DNA-FISH, Western blotting, flow cytometry, and phenotypic analyses. Results: Multiomics analysis revealed extensive chromatin remodeling during LEC-to-LFC differentiation, including A/B compartment switching, silencer reprogramming, and transcriptional changes in differentiation- and apoptosis-related genes. A specific loop tethering Blcap to the DSR was identified in LFCs. Loop disruption abolished their spatial proximity, derepressed Blcap, reduced anti-apoptotic genes Bcl2 and Bcl2l1, increased apoptosis, and caused lens opacification. Conclusions: The Blcap-DSR chromatin loop plays a key protective role by repressing Blcap and maintaining anti-apoptotic balance in LFCs. Through silencer-associated looping and epigenetic reprogramming, LFCs achieve controlled nuclear and organelle clearance without triggering cell death, ensuring proper differentiation and lens transparency.
Indexed as
Identifiers
What Socratic holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.