OSCR

Stress Responsive bZIP Transcription Factors ATF4 and BACH1 Cooperate With MAF-Family bZIP Protein NRL to Fine-Tune Rod Photoreceptor Gene Expression.

Code ↔ Paper

8 matches between paragraphs of the paper and lines of its authors' code, computed by the harvester (lexical-v1). Click a colored paragraph or line to see its counterpart.

The 8 matches
  1. [1] § Methods › CUT&Tag Analysis ↔ CUT-Tag/CUT-Tag.Rmd, lines 56–76 · score 0.80 · Consensus peaks, CUT Tag, gene promoters, SEACR, bedtools, intersect
  2. [2] § Methods › Single-Cell RNA Sequencing Analysis ↔ scRNAseq/00_Data_Import.Rmd, lines 265–324 · score 0.79 · Extracellular matrix cells, Retinal pigment epithelial, Fibroblasts, Astrocytes, scType, imported
  3. [3] § Results › ATF4 and BACH1 Bind Phototransduction Gene Promotors In Vivo ↔ CUT-Tag/CUT-Tag.Rmd, lines 56–76 · score 0.71 · gene promoter regions, BACH1 peaks, ATF4 peaks, CUT Tag, Promotors, NRL
  4. [4] § Results › ATF4 and BACH1 Bind Phototransduction Gene Promotors In Vivo ↔ CUT-Tag/CUT-Tag.Rmd, lines 79–108 · score 0.68 · pairwise_termsim, bound promoters, bound genes, gene promoters, Reactome, pathway
  5. [5] § Methods › Single-Cell RNA Sequencing Analysis ↔ scRNAseq/02_DE_Analysis.Rmd, lines 252–299 · score 0.67 · FindMarkers, logfc.threshold, min.pct, DGE, Seurat, filtered
  6. [6] § Results › ATF4 Expression Correlates With Phototransduction Activity and Rod Photoreceptor Specialization ↔ scRNAseq/02_DE_Analysis.Rmd, lines 114–209 · score 0.58 · decontXcounts, rod cluster, Atf4 expression, horizontal, violin, UMAP
  7. [7] § Results › ATF4 Expression Correlates With Phototransduction Activity and Rod Photoreceptor Specialization ↔ scRNAseq/02_DE_Analysis.Rmd, lines 34–71 · score 0.54 · CUT Tag peaks, scRNA, seq, promoter, Rod, Atf4
  8. [8] § Results › ATF4 and BACH1 Bind Phototransduction Gene Promotors In Vivo ↔ CUT-Tag/CUT-Tag.Rmd, lines 79–108 · score 0.53 · BACH1 bound gene, ATF4 bound gene, gene promoters, enriched, NRL

Paper

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The authors' code

R Markdown · 108 lines · 4.3 KB · no license · 4 matches

  1. ---
  2. title: "CUT&Tag analysis"
  3. output: html_document
  4. author: "Zachary Batz
  5. date: "2025-11-20"
  6. ---
  9. ### R
  10. ```{r}
  11. ## Find mouse the TSS and promoter locations for protein coding genes (ensembl 102)
  12. library(AnnotationHub)
  13. library(ensembldb)
  14. library(dplyr)
  16. ## Set variables
  17. ## ensembl 102 is the last one to use mm10
  18. release <- 102
  20. ## Load annotation
  21. anno <- query(AnnotationHub(), pattern=c("Mus musculus", "EnsDb", release))[[1]]
  23. ## Pull protein coding TSS locations
  24. transcripts(anno)
  25. TSS <- promoters(transcripts(anno), upstream=0, downstream=0)
  26. TSS <- trim(TSS)[, c("gene_id","tx_id","tx_name", "tx_biotype")]
  27. TSS <- data.frame(TSS) %>% dplyr::filter(tx_biotype == "protein_coding")
  30. ## Pull protein coding gene promoters
  31. proms <- promoters(genes(anno), upstream=1000, downstream=500)
  32. proms <- trim(proms)[, c("symbol","gene_id","gene_biotype")]
  33. proms <- data.frame(proms) %>% dplyr::filter(gene_biotype == "protein_coding")
  35. ## Write out the table as a bed file
  36. data.frame(TSS) %>% dplyr::select(
  37. seqnames,
  38. start, end, tx_id, gene_id
  39. ) %>% dplyr::mutate(seqnames = paste0("chr",seqnames)) %>%
  40. dplyr::mutate(gene = paste0(gene_id,"_",tx_id)) %>%
  41. dplyr::select(-gene_id) %>%
  42. write.table("mouse_TSS_ensemblv102.bed", sep = '\t', quote = F, row.names = F, col.names = F)
  44. data.frame(proms) %>% dplyr::select(
  45. seqnames,
  46. start, end, symbol, gene_id
  47. ) %>% dplyr::mutate(seqnames = paste0("chr",seqnames)) %>%
  48. dplyr::mutate(gene = paste0(symbol,"_",gene_id)) %>%
  49. dplyr::select(-symbol,-gene_id) %>%
  50. write.table("mouse_promoters_ensemblv102.bed", sep = '\t', quote = F, row.names = F, col.names = F)
  52. ```
  56. ### Command line
  57. ```{bash}
  58. ## Identify Shared Peaks (present in at least 2 of 3 samples)
  59. bedtools multiinter -i Atf4_R1.seacr.peaks.stringent.bed Atf4_R2.seacr.peaks.stringent.bed Atf4_R3.seacr.peaks.stringent.bed | awk '{if ($4>1) {print} }' > Atf4_peaks.bed
  60. bedtools multiinter -i Nrl_R1.seacr.peaks.stringent.bed Nrl_R2.seacr.peaks.stringent.bed Nrl_R3.seacr.peaks.stringent.bed | awk '{if ($4>1) {print} }' > Nrl_peaks.bed
  61. bedtools multiinter -i Bach1_R1.seacr.peaks.stringent.bed Bach1_R2.seacr.peaks.stringent.bed Bach1_R3.seacr.peaks.stringent.bed | awk '{if ($4>1) {print} }' > Bach1_peaks.bed
  63. ## Sort TSS sites and promotoers for bedtools
  64. sort -k1,1 -k2,2n mouse_TSS_ensemblv102.bed > mouse_TSS_ensemblv102.sorted.bed
  65. sort -k1,1 -k2,2n mouse_promoters_ensemblv102.bed > mouse_promoters_ensemblv102.sorted.bed
  67. ## Find the closest protein coding TSS for each consensus peak for Atf4 and Bach1
  68. bedtools closest -a Atf4_peaks.bed -b mouse_TSS_ensemblv102.sorted.bed -d > Atf4_closest_TSS.txt
  69. bedtools closest -a Bach1_peaks.bed -b mouse_TSS_ensemblv102.sorted.bed -d > Bach1_closest_TSS.txt
  71. ## Find genes with peaks bound to promoter regions
  72. bedtools intersect -a Atf4_peaks.bed -b mouse_promoters_ensemblv102.sorted.bed -wb > Atf4_bound_gene_promoters.bed
  73. bedtools intersect -a Bach1_peaks.bed -b mouse_promoters_ensemblv102.sorted.bed -wb > Bach1_bound_gene_promoters.bed
  74. bedtools intersect -a Nrl_peaks.bed -b mouse_promoters_ensemblv102.sorted.bed -wb > Nrl_bound_gene_promoters.bed
  76. ```
  79. ### R
  80. ```{r}
  81. ## Enrichment analysis
  82. library(dplyr)
  83. library(clusterProfiler)
  84. library(ReactomePA)
  85. library(GOSemSim)
  87. ## Identify genes with Atf4 and Nrl bound promoters
  88. atf4_genes <- read.table("Atf4_bound_gene_promoters.bed")
  89. nrl_genes <- read.table("Nrl_bound_gene_promoters.bed")
  90. atf4_nrl_genes <- atf4_genes %>% filter(gene %in% nrl_genes$gene)
  92. ## Identify genes with Bach1 and Nrl bound promoters
  93. bach1_genes <- read.table("Bach1_bound_gene_promoters.bed")
  94. bach1_nrl_genes <- bach1_genes %>% filter(gene %in% nrl_genes$gene)
  97. ## Perform enrichment analyses
  98. atf4_nrl_entrez <- bitr(atf_nrl$gene, fromType = "ENSEMBL", toType = "ENTREZID", OrgDb = "org.Mm.eg.db")
  99. atf4_nrl_res <- enrichPathway(gene=atf4_nrl_entrez$V1, pvalueCutoff=0.05, readable = T, organism = "mouse")
  100. dotplot(atf4_nrl_res)
  101. atf4_nrl_res$result %>% write.table("atf4_nrl_reactome_enrichment", sep='\t', quote = F, row.names=F)
  103. bach1_nrl_res <- enrichGO(genes = bach1_nrl_genes$gene, OrgDb = org.Mm.eg.db, keyType = "ENSEMBL", ont = "BP", pvalueCutoff = 0.01, qvalueCutoff = 0.01, readable = T)
  104. bach1_nrl_res_sim <- pairwise_termsim(bach1_nrl_res)
  105. treeplot(bach1_nrl_res_sim, hclust_method = "average")
  106. bach1_nrl_res$result %>% write.table("bach1_nrl_gobp_enrichment", sep='\t', quote = F, row.names=F)
  108. ```

CUT-Tag.Rmd at commit 939e51f, no license · at the source

Overview

Authors: Kiam Preston Jr1,2, Madhuri Arya1, Anjani Kumari1, Jacob Nellissery1, Matthew J Brooks1, Zachary Batz1, Xulong Liang1, Gianluca Tosini2, Anand Swaroop1
  1. Neurobiology, Neurodegeneration and Repair Laboratory, National Eye Institute, National Institutes of Health, Bethesda, Maryland, United States
  2. Department of Pharmacology and Toxicology and Neuroscience Institute, Morehouse School of Medicine, Atlanta, Georgia, United States
Institutions: National Institutes of Health (United States); National Eye Institute (United States); Morehouse School of Medicine (United States)
Journal: Investigative ophthalmology & visual science, volume 67, issue 6, article 9
Dates: received 10 February 2026; accepted 18 May 2026; published online 5 June 2026; in print June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1167/iovs.67.6.9 · PMID 42246540 · PMCID PMC13249099 · OpenAlex W7163661761
Open access: gold, a free copy (OpenAlex)
Status: code verified
Categories: genetics / omics (modality), human (organism), mouse (organism), cellular / molecular (subfield)
Methods: Statistics, Smoothing, state filtering, decompositions, Evoked potentials
Keywords: gene regulation, protein–protein interaction, retina, stress response, yeast two hybrid
MeSH: Activating Transcription Factor 4*, Basic-Leucine Zipper Transcription Factors*, Eye Proteins*, Gene Expression Regulation*, Retinal Rod Photoreceptor Cells*, Animals, Humans, Immunoprecipitation, Mice, Mice, Inbred C57BL, Two-Hybrid System Techniques (* major topic)
Topic: Retinal Development and Disorders (Molecular Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Citations: not cited yet (Europe PMC); 65 references in the paper
Research resources: RRID:AB_2535792, RRID:AB_2535853

Abstract

Purpose: Musculoaponeurotic fibrosarcoma (MAF) family basic motif leucine zipper (bZIP) transcription factor neural retina leucine zipper (NRL) determines rod cell fate and controls expression of rod genes in concert with multiple regulatory proteins. Mutations in NRL, its targets, and interacting proteins are associated with retinopathies. Because bZIP heterodimerization expands target sequence selectivity, we set out to identify bZIP protein interactors of NRL.

Methods: Interactors were identified by yeast two-hybrid and co-immunoprecipitation, validated by high-resolution microscopy and proximity ligation, and functionally assessed by reporter assays. We used Cleavage Under Targets and Tagmentation (CUT&Tag) to map activating transcription factor 4 (ATF4) and BTB and CNC homology 1 (BACH1) occupancy and single-cell RNA sequencing (scRNA-seq) to assess gene expression changes in response to their knockdown in mouse retina.

Results: We identified two bZIP proteins, ATF4 and BACH1, as interactors of NRL. We demonstrate a direct interaction of NRL and ATF4 via leucine zipper domain and validate their co-localization in rod photoreceptors. NRL and BACH1 are also partially colocalized, but their interaction likely requires additional factors. Reporter assays show that ATF4 promotes NRL-mediated transactivation of rhodopsin promoter, whereas BACH1 appears to act as a suppressor. CUT&Tag revealed shared and distinct binding sites for NRL, ATF4, and BACH1 in promoters of rod-expressed genes, including phototransduction genes. scRNA-seq further indicated a concordance of higher ATF4 and NRL expression with upregulation of phototransduction genes in distinct rod subpopulations.

Conclusions: We suggest that the NRL-mediated gene regulatory network includes transient and stable but context-dependent protein–protein interactions, which control quantitatively precise gene expression patterns in mature rod photoreceptors. Our findings suggest therapeutic potential for retinopathies involving photoreceptor dysfunction through targeted gene expression modulation.

Reproduced under the paper's license (CC BY), from the paper cited above.

Repositories

Its files are read in the Code ↔ Paper reader above, with 8 matches between paragraphs and lines of code.

mbrooks313/scrna-seq

License: none: the authors keep all their rights
State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: f93d230623822f27fc77ef087e53c104681c6af3, 10 November 2025
Languages: R (13), Python (3), Shell (2)
Size: 27 files, 18 scripts
Software Heritage: not archived
Found in: the text, “Single-Cell RNA Sequencing Analysis”
Holds: README, 4 notebooks
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: Seurat (9 files), tidyverse (8 files), cowplot (5 files), pandas (3 files), Snakemake (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
19 files
At the source: github.com/MBrooks313/scRNA-seq/blob/main/annotation/Retina_Cell_type_MB_v4.xlsx

NEI-NNRL/2025_Preston_Atf4

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State: the link answers, verified on 27 September 2026
Evidence: files inventoried
Commit: 939e51f365a3e2f1c70c6042a175cadbb6586b44, 20 November 2025
Languages: R (4)
Size: 6 files, 4 scripts
Software Heritage: not archived
Found in: the acknowledgements
Holds: README, 4 notebooks
Not found: license file, CITATION.cff, environment file, tests, continuous integration, documentation
Tools: tidyverse (4 files), cowplot (3 files), Seurat (3 files), clusterProfiler (2 files), ggplot2 (2 files), BEDTools (1 file)
Availability: 1 check, the latest on 27 September 2026: the link answers
  • 27 September 2026: the link answers
5 files
At the source: github.com/NEI-NNRL/2025_Preston_Atf4

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What the map holds:

  • 2 repositories of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
  • 22 scripts, each with its path and the digest of its content;
  • 8 matches between paragraphs of the paper and lines of the code (method lexical-v1);
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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 9 authors, 5 keywords, 11 MeSH terms, 65 references, 2 RRIDs.

Cite

This paper

Preston, K., Arya, M., Kumari, A., Nellissery, J., Brooks, M. J., Batz, Z., Liang, X., Tosini, G., & Swaroop, A. (2026). 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, 67(6), 9. https://doi.org/10.1167/iovs.67.6.9

BibTeX

@article{preston2026stress,
author = {Preston, Kiam and Arya, Madhuri and Kumari, Anjani and Nellissery, Jacob and Brooks, Matthew J and Batz, Zachary and Liang, Xulong and Tosini, Gianluca and Swaroop, Anand},
title = {{Stress Responsive bZIP Transcription Factors ATF4 and BACH1 Cooperate With MAF-Family bZIP Protein NRL to Fine-Tune Rod Photoreceptor Gene Expression}},
journal = {Investigative ophthalmology \& visual science},
year = {2026},
month = jun,
volume = {67},
number = {6},
pages = {9},
publisher = {Association for Research in Vision and Ophthalmology},
issn = {0146-0404},
doi = {10.1167/iovs.67.6.9},
url = {https://doi.org/10.1167/iovs.67.6.9},
pmid = {42246540},
pmcid = {PMC13249099}
}

RIS

TY - JOUR
AU - Preston, Kiam
AU - Arya, Madhuri
AU - Kumari, Anjani
AU - Nellissery, Jacob
AU - Brooks, Matthew J
AU - Batz, Zachary
AU - Liang, Xulong
AU - Tosini, Gianluca
AU - Swaroop, Anand
TI - Stress Responsive bZIP Transcription Factors ATF4 and BACH1 Cooperate With MAF-Family bZIP Protein NRL to Fine-Tune Rod Photoreceptor Gene Expression
T2 - Investigative ophthalmology & visual science
J2 - Invest Ophthalmol Vis Sci
PY - 2026
DA - 2026/06/01
VL - 67
IS - 6
SP - 9
SN - 0146-0404
PB - Association for Research in Vision and Ophthalmology
DO - 10.1167/iovs.67.6.9
UR - https://doi.org/10.1167/iovs.67.6.9
LA - en
ER -

CSL-JSON

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