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Immediate early genes (IEGs), identified by their rapid stress-induced transient bursts of expression, are critical to integrating downstream signaling pathways. In studying tumor initiation by patient-derived breast cancer cells, we observed acquisition of open chromatin domains at the genebody and 3’-UTR of IEGs, uniquely across the genome. Through in vivo and in vitro modeling, we show that the IEG and orphan nuclear receptor NR4A1 localizes across multiple IEG genebodies, where it binds to RNA Pol II, arresting transcriptional elongation and generating extensive R-loops and accessible chromatin. Acute stress promptly removes NR4A1 from IEG genebodies, triggering immediate release of their poised transcripts. In breast cancer cells, NR4A1 overexpression increases tumorigenesis conversely, its deletion leads to uncompensated replication stress, chromosomal instability and mitotic catastrophe, driven by deregulation of its IEG target FOS. A large fraction of primary breast and other cancers exhibit open genebody chromatin at IEGs, consistent with preserved NR4A1 function. Thus, NR4A1 mediates a novel transcriptional elongation checkpoint, unique to stress-induced genes and required for their rapid bursts of expression. Cancers that have retained this mechanism in adapting to chronic replication stress may be dependent on NR4A1 for proliferation. Overall design: In this study, we sequenced 12 ATAC-seq samples, including 4 samples of BRx142 CTC cells, 4 samples of BRx82 CTC cells and 4 samples of MCF10A cells with or without RNAseH1 overexpression."],"repository":["ENA"],"description_synonyms":["ChIP-Chip, Materials, Nur77, Chromatin Immuno-precipitation, n10, hmr, Neoplasms, Benign Neoplasm, Gene, CLIP-Seq, Hbr-1, Assay for Transposase-Accessible Chromatin Using Sequencing, Tumor, Malignant, Chromatin Immunoprecipitation Sequencing-Chip, DmF2, Fs(3)Hor, lod, Chromatin Immunoprecipitation Sequencing Chip, NP10, DmelCG2684, Chromatin Immuno precipitation Sequencing, Genetic, Malignancy, ChIP, Chromatin Immunoprecipitation Paired End Tag, ATAC-seq, Chromatin Immuno Precipitation Paired End Tag, np10, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, TIS1, NTef2, Gfrp, Sequencing, Chromatin Immunoprecipitation Paired-End Tag, Neoplasias, malignant neoplasm, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, TR3, tr3, Malignancies, GFRP1, Cancer, Tumors, HITS-CLIP, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, nak-1, Malignant Neoplasm, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, ChIP Sequencing, Cistrons, ChIP-PET, ChIP-Exo, Fs(3)Sz11, MT, Benign, gfrp1, Neoplasm, Genetic Materials, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, Hbr1, Genetic Material, Ngfi-b, primary cancer, ATAC-seq assay, NGFI-B, Benign Neoplasms, Chromatin Immunoprecipitation, INSDC_feature:gene, Chromatin Immuno-precipitation Sequencing, Cancers, ChIP Exonuclease, Lds, ChIP-Seq, malignant tumor, early, Assay for Transposase Accessible Chromatin Using Sequencing, Malignant Neoplasms, ngf1b, NGFIB, Material, nr4a1-A, Horka, ChIA-PET., HMR, N10, Hmr, Chromatin Immuno-Precipitation Paired-End Tag, nur77, CG2684, Fs(3)Horka, Cistron, NAK-1, NUR77, ChIP-Exonuclease, Neoplasia"],"name_synonyms":["ChIP-Chip, Materials, Nur77, Chromatin Immuno-precipitation, n10, hmr, Neoplasms, Benign Neoplasm, Gene, CLIP-Seq, Hbr-1, Assay for Transposase-Accessible Chromatin Using Sequencing, Tumor, Malignant, Chromatin Immunoprecipitation Sequencing-Chip, DmF2, Fs(3)Hor, lod, Chromatin Immunoprecipitation Sequencing Chip, NP10, DmelCG2684, Chromatin Immuno precipitation Sequencing, Genetic, Malignancy, ChIP, Chromatin Immunoprecipitation Paired End Tag, ATAC-seq, Chromatin Immuno Precipitation Paired End Tag, np10, Cross-Linking and Immunoprecipitation Followed by Deep Sequencing, TIS1, NTef2, Gfrp, Sequencing, Chromatin Immunoprecipitation Paired-End Tag, Neoplasias, malignant neoplasm, ATAC-Seq, Chromatin Immunoprecipitation Sequencing-Chips, TR3, tr3, Malignancies, GFRP1, Cancer, Tumors, HITS-CLIP, High Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, nak-1, Malignant Neoplasm, Cross Linking and Immunoprecipitation Followed by Deep Sequencing, ChIP Sequencing, Cistrons, ChIP-PET, ChIP-Exo, Fs(3)Sz11, MT, Benign, gfrp1, Neoplasm, Genetic Materials, High-Throughput Sequencing of RNA Isolated by Crosslinking Immunoprecipitation, Hbr1, Genetic Material, Ngfi-b, primary cancer, ATAC-seq assay, NGFI-B, Benign Neoplasms, Chromatin Immunoprecipitation, INSDC_feature:gene, Chromatin Immuno-precipitation Sequencing, Cancers, ChIP Exonuclease, Lds, ChIP-Seq, malignant tumor, early, Assay for Transposase Accessible Chromatin Using Sequencing, Malignant Neoplasms, ngf1b, NGFIB, Material, nr4a1-A, Horka, ChIA-PET., HMR, N10, Hmr, Chromatin Immuno-Precipitation Paired-End Tag, nur77, CG2684, Fs(3)Horka, Cistron, NAK-1, NUR77, ChIP-Exonuclease, Neoplasia"],"additional_accession":[]},"is_claimable":false,"name":"NR4A1 suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation [ATAC-seq]","description":"NR4A1 suppresses cancer replication stress through R-loop-dependent inhibition of immediate early gene transcriptional elongation [ATAC-seq]","dates":{"last_updated":"2025-09-24","first_public":"2021-11-05"},"accession":"PRJNA679341","cross_references":{"GEO":["GSE161782"],"taxon":["9606"],"PubMed":["34624217"]}}