ArticleHuman molecular genetics2022
Developmental genome-wide occupancy analysis of bZIP transcription factor NRL uncovers the role of c-Jun in early differentiation of rod photoreceptors in the mammalian retina.
Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 17 citations in OpenAlex.
- Stress Responsive bZIP Transcription Factors ATF4 and BACH1 Cooperate With MAF-Family bZIP Protein NRL to Fine-Tune Rod Photoreceptor Gene Expression.Investigative ophthalmology & visual science · 2026Article
- Lactate and histone H3K18 lactylation are associated with metabolic control of gene expression in the retina.PLoS genetics · 2026Article
- A robust cis-regulatory network ensures Otx2 expression during retinal development.Development (Cambridge, England) · 2026Article
- Regulatory role of the circHIPK3/miR-125a-5p/NDUFA5 axis in diabetic retinopathy: combined analysis of single-cell and bulk transcriptomes.American journal of translational research · 2026Article
- Aerobic glycolysis and lactate regulate histone H3K18Lactylation occupancy to fine-tune gene expression in developing and mature retina.bioRxiv : the preprint server for biology · 2025Article
- Article
- CTCF regulates global chromatin accessibility and transcription during rod photoreceptor development.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Murine Retina Outer Plexiform Layer Development and Transcriptome Analysis of Pre-Synapses in Photoreceptors.Life (Basel, Switzerland) · 2024Article
- Protein kinase CK2 modulates the activity of Maf-family bZIP transcription factor NRL in rod photoreceptors of mammalian retina.Human molecular genetics · 2023Article
- Disease-causing mutations in genes encoding transcription factors critical for photoreceptor development.Frontiers in molecular neuroscience · 2023Review
- Inhibition of the MAPK/c-Jun-EGR1 Pathway Decreases Photoreceptor Cell Death in theInternational journal of molecular sciences · 2022Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The basic motif-leucine zipper (bZIP) transcription factor neural retina leucine zipper (NRL) determines rod photoreceptor cell fate during retinal development, and its loss leads to cone-only retina in mice. NRL works synergistically with homeodomain protein Cone-Rod Homeobox and other regulatory factors to control the transcription of most genes associated with rod morphogenesis and functional maturation, which span over a period of several weeks in the mammalian retina. We predicted that NRL gradually establishes rod cell identity and function by temporal and dynamic regulation of stage-specific transcriptional targets. Therefore, we mapped the genomic occupancy of NRL at four stages of mouse photoreceptor differentiation by CUT&RUN analysis. Dynamics of NRL binding revealed concordance with the corresponding changes in transcriptome of the developing rods. Notably, we identified c-Jun proto-oncogene as one of the targets of NRL, which could bind to specific cis-elements in the c-Jun promoter and modulate its activity in HEK293 cells. Coimmunoprecipitation studies showed the association of NRL with c-Jun, also a bZIP protein, in transfected cells as well as in developing mouse retina. Additionally, shRNA-mediated knockdown of c-Jun in the mouse retina in vivo resulted in altered expression of almost 1000 genes, with reduced expression of phototransduction genes and many direct targets of NRL in rod photoreceptors. We propose that c-Jun-NRL heterodimers prime the NRL-directed transcriptional program in neonatal rod photoreceptors before high NRL expression suppresses c-Jun at later stages. Our study highlights a broader cooperation among cell-type restricted and widely expressed bZIP proteins, such as c-Jun, in specific spatiotemporal contexts during cellular differentiation.
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