ArticlePLoS genetics2012
Transcriptional regulation of rod photoreceptor homeostasis revealed by in vivo NRL targetome analysis.
Article in PLoS genetics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.
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Who cites it
80 citing papers in PubMed, 123 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
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- Molecular basis of CRX/DNA recognition and stoichiometry at the Ret4 response element.Structure (London, England : 1993) · 2024Article
- Murine Retina Outer Plexiform Layer Development and Transcriptome Analysis of Pre-Synapses in Photoreceptors.Life (Basel, Switzerland) · 2024Article
- Phototactic preference and its genetic basis in the planulae of the colonial HydrozoanbioRxiv : the preprint server for biology · 2024Article
- Transcription factor interactions explain the context-dependent activity of CRX binding sites.PLoS computational biology · 2024Article
- Unleashing the potential of CRISPR multiplexing: Harnessing Cas12 and Cas13 for precise gene modulation in eye diseases.Vision research · 2023Review
- Molecular mechanisms controlling vertebrate retinal patterning, neurogenesis, and cell fate specification.Trends in genetics : TIG · 2023Review
- Rho enhancers play unexpectedly minor roles in Rhodopsin transcription and rod cell integrity.Scientific reports · 2023Article
- Mammalian cargo receptors for endoplasmic reticulum-to-Golgi transport: mechanisms and interactions.Biochemical Society transactions · 2023Review
- 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
- Blimp-1/PRDM1 and Hr3/RORβ specify the blue-sensitive photoreceptor subtype inFrontiers in cell and developmental biology · 2023Article
- Polyglutamine-expanded ATXN7 alters a specific epigenetic signature underlying photoreceptor identity gene expression in SCA7 mouse retinopathy.Journal of biomedical science · 2022Article
- 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.Human molecular genetics · 2022Article
- Interaction of human CRX and NRL in live HEK293T cells measured using fluorescence resonance energy transfer (FRET).Scientific reports · 2022Article
- Rod genesis driven by mafba in an nrl knockout zebrafish model with altered photoreceptor composition and progressive retinal degeneration.PLoS genetics · 2022Article
- Novel homozygous mutations in the transcription factorMolecular vision · 2022Article
- Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 2 countries.
Funding
Abstract
A stringent control of homeostasis is critical for functional maintenance and survival of neurons. In the mammalian retina, the basic motif leucine zipper transcription factor NRL determines rod versus cone photoreceptor cell fate and activates the expression of many rod-specific genes. Here, we report an integrated analysis of NRL-centered gene regulatory network by coupling chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) data from Illumina and ABI platforms with global expression profiling and in vivo knockdown studies. We identified approximately 300 direct NRL target genes. Of these, 22 NRL targets are associated with human retinal dystrophies, whereas 95 mapped to regions of as yet uncloned retinal disease loci. In silico analysis of NRL ChIP-Seq peak sequences revealed an enrichment of distinct sets of transcription factor binding sites. Specifically, we discovered that genes involved in photoreceptor function include binding sites for both NRL and homeodomain protein CRX. Evaluation of 26 ChIP-Seq regions validated their enhancer functions in reporter assays. In vivo knockdown of 16 NRL target genes resulted in death or abnormal morphology of rod photoreceptors, suggesting their importance in maintaining retinal function. We also identified histone demethylase Kdm5b as a novel secondary node in NRL transcriptional hierarchy. Exon array analysis of flow-sorted photoreceptors in which Kdm5b was knocked down by shRNA indicated its role in regulating rod-expressed genes. Our studies identify candidate genes for retinal dystrophies, define cis-regulatory module(s) for photoreceptor-expressed genes and provide a framework for decoding transcriptional regulatory networks that dictate rod homeostasis.
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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 OpenQuestion graph.