RNA-dependent CUT&RUN (rCUT&RUN) of MYC and TBP in MCF-7 cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE252694 | GEO | 2025/05/08
REPOSITORIES: GEO
Similar Datasets
Project description:MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs binding to MYC enhance its chromatin occupancy. This process helps on MYC-mediated regulation of gene expression. Mechanistically, Lys355, Arg356, and Arg357 in the basic region of MYC are essential for RNA binding. Alanine mutation of these three amino acids abolishes MYC RNA-binding function but causes minimal damage to MYC/MAX DNA-binding capacity. Only loss of MYC RNA-binding function, while maintaining DNA-binding function, significantly decreases MYC chromatin occupancy in vivo. Our study reveals a new dimension to MYC-mediated gene regulation by demonstrating that RNA-binding activity plays an important role in MYC’s function.
2025-05-08 | GSE252697 | GEO
Project description:MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs binding to MYC enhance its chromatin occupancy. This process helps on MYC-mediated regulation of gene expression. Mechanistically, Lys355, Arg356, and Arg357 in the basic region of MYC are essential for RNA binding. Alanine mutation of these three amino acids abolishes MYC RNA-binding function but causes minimal damage to MYC/MAX DNA-binding capacity. Only loss of MYC RNA-binding function, while maintaining DNA-binding function, significantly decreases MYC chromatin occupancy in vivo. Our study reveals a new dimension to MYC-mediated gene regulation by demonstrating that RNA-binding activity plays an important role in MYC’s function.
2025-05-08 | GSE252696 | GEO
Project description:MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs binding to MYC enhance its chromatin occupancy. This process helps on MYC-mediated regulation of gene expression. Mechanistically, Lys355, Arg356, and Arg357 in the basic region of MYC are essential for RNA binding. Alanine mutation of these three amino acids abolishes MYC RNA-binding function but causes minimal damage to MYC/MAX DNA-binding capacity. Only loss of MYC RNA-binding function, while maintaining DNA-binding function, significantly decreases MYC chromatin occupancy in vivo. Our study reveals a new dimension to MYC-mediated gene regulation by demonstrating that RNA-binding activity plays an important role in MYC’s function.
2025-05-08 | GSE252695 | GEO
Project description:Transcription factor (TF) MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs that bind to MYC increase MYC’s chromatin occupancy, which helps with MYC-mediated regulation of gene expression. Mechanistically, two highly conserved sequences, amino acids 355-357 and 364-367, in the basic region of MYC are essential for RNA binding. Notably, alanine substitution of Lys355, Arg356, and Arg357 of MYC abolishes its RNA binding function but does not influence its complex formation ability, and E-box binding capacity of MYC:MAX dimer in vitro. However, loss of RNA binding function alone decreases MYC recruitment at gene regulatory elements in vivo, followed by a decreased MYC:MAX chromatin binding at these regions. This process further attenuates MYC-mediated gene expression. Therefore, RNA-binding-deficient MYC is compromised in promoting cancer cell proliferation. By demonstrating the mechanism of MYC-RNA interaction and the fundamental role of RNA binding activity in MYC-centric functions, our study reveals a new paradigm to MYC function and highlights an essential and probably general role of RNA binding capacity of TFs for their gene regulatory function.
2025-05-08 | GSE273776 | GEO
Project description:Transcription factor (TF) MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs that bind to MYC increase MYC’s chromatin occupancy, which helps with MYC-mediated regulation of gene expression. Mechanistically, two highly conserved sequences, amino acids 355-357 and 364-367, in the basic region of MYC are essential for RNA binding. Notably, alanine substitution of Lys355, Arg356, and Arg357 of MYC abolishes its RNA binding function but does not influence its complex formation ability, and E-box binding capacity of MYC:MAX dimer in vitro. However, loss of RNA binding function alone decreases MYC recruitment at gene regulatory elements in vivo, followed by a decreased MYC:MAX chromatin binding at these regions. This process further attenuates MYC-mediated gene expression. Therefore, RNA-binding-deficient MYC is compromised in promoting cancer cell proliferation. By demonstrating the mechanism of MYC-RNA interaction and the fundamental role of RNA binding activity in MYC-centric functions, our study reveals a new paradigm to MYC function and highlights an essential and probably general role of RNA binding capacity of TFs for their gene regulatory function.
2025-05-08 | GSE273775 | GEO
Project description:Transcription factor (TF) MYC binds to thousands of gene regulatory elements in the genome such as promoters and enhancers and exerts an amplification effect on the expression of most genes, regardless of the E-box motif existence. In this study, we discovered that MYC is an RNA-binding protein with a high affinity to guanosine-rich RNAs. RNAs that bind to MYC increase MYC’s chromatin occupancy, which helps with MYC-mediated regulation of gene expression. Mechanistically, two highly conserved sequences, amino acids 355-357 and 364-367, in the basic region of MYC are essential for RNA binding. Notably, alanine substitution of Lys355, Arg356, and Arg357 of MYC abolishes its RNA binding function but does not influence its complex formation ability, and E-box binding capacity of MYC:MAX dimer in vitro. However, loss of RNA binding function alone decreases MYC recruitment at gene regulatory elements in vivo, followed by a decreased MYC:MAX chromatin binding at these regions. This process further attenuates MYC-mediated gene expression. Therefore, RNA-binding-deficient MYC is compromised in promoting cancer cell proliferation. By demonstrating the mechanism of MYC-RNA interaction and the fundamental role of RNA binding activity in MYC-centric functions, our study reveals a new paradigm to MYC function and highlights an essential and probably general role of RNA binding capacity of TFs for their gene regulatory function.
2025-05-08 | GSE273777 | GEO
Project description:MYC has been known to bind to thousands of promoters and exert an amplification effect on expression of most genes. Meanwhile, MYC drives tumorigenesis through the regulation of a unique set of cancer-specific targets that differ from its targets in normal cells. However, the mechanism underlying this discrepancy in MYC’s regulation in tumor and normal cells has not been fully elucidated. In this study, we discovered that MYC protein has a broad RNA binding spectrum including promoter-associated RNAs (paRNAs) and enhancer RNAs (eRNAs). MYC’s RNA binding peaks colocalize with its DNA binding sites, but not dependent on its HLHLZ domain or transcription activation domain. By further integrating multiple dimensional data from cancer cells and tumors samples, we have shown that the MYC-bound paRNAs and eRNAs can shape MYC chromatin interaction to regulate gene transcription. Finally, we have mechanistically characterized a MYC-bound eRNA, MERG1, that plays essential roles in the ERα+ breast cancer tumorigenesis. Mechanistically, MERG1 interacts with MYC and enhances MYC’s binding to the enhancer and promoter of GREB1 gene. This process specifically amplifies the target gene GREB1 expression and accelerates tumor progression. Our study demonstrates that MYC’s interaction with paRNAs and eRNAs contribute to its specific amplification of gene expression in tumorigenesis.
2025-04-30 | GSE200163 | GEO
Project description:The c-Myc HLH-bZIP protein has been implicated in physiological or pathological growth, proliferation, apoptosis, metabolism and differentiation at the cellular, tissue or organismal levels via regulation of numerous target genes. In part due to the incomplete inventory and functional accounting of Myc’s targets, no principle unifies Myc action. To relate the dynamics of Myc-binding with target expression and function in a system where Myc-levels are temporally and physiologically regulated, the transcriptomes and the genome-wide distributions of Myc, RNA polymerase II and chromatin modifications were compared during lymphocyte activation and in ES cells. A remarkably simple rule emerged from this quantitative analysis: Myc is not an on-off switch, but is a non-linear amplifier of expression, acting universally at active genes, except for immediate early genes that are strongly induced before Myc. This rule of Myc action explains the vast majority of Myc biology observed in literature. Quiescent B-cells (B0) were treated with lipopolysaccharide (LPS) for 4 hrs (B4), and resting T-cells (T0) were activated with conA for 4 hrs (T4) and for 14 hrs (T14). Following treatments, RNA was harvested and chromatin was prepared at these time points. The RNA was analyzed by hybridization with Affymetrix microarrays.
2012-09-27 | E-GEOD-37222 | biostudies-arrayexpress
Project description:The c-Myc HLH-bZIP protein has been implicated in physiological or pathological growth, proliferation, apoptosis, metabolism and differentiation at the cellular, tissue or organismal levels via regulation of numerous target genes. In part due to the incomplete inventory and functional accounting of Myc’s targets, no principle unifies Myc action. To relate the dynamics of Myc-binding with target expression and function in a system where Myc-levels are temporally and physiologically regulated, the transcriptomes and the genome-wide distributions of Myc, RNA polymerase II and chromatin modifications were compared during lymphocyte activation and in ES cells. A remarkably simple rule emerged from this quantitative analysis: Myc is not an on-off switch, but is a non-linear amplifier of expression, acting universally at active genes, except for immediate early genes that are strongly induced before Myc. This rule of Myc action explains the vast majority of Myc biology observed in literature. Quiescent B-cells (B0) were treated with lipopolysaccharide (LPS) for 4 hrs (B4), and resting T-cells (T0) were activated with conA for 4 hrs (T4) and for 14 hrs (T14). Following treatments, RNA was harvested and chromatin was prepared at these time points. The chromatin was immunoprecipitated using anti-EGFP antibodies and analyzed by ChIP-seq.
2012-09-27 | E-GEOD-37229 | biostudies-arrayexpress
Project description:The c-Myc HLH-bZIP protein has been implicated in physiological or pathological growth, proliferation, apoptosis, metabolism and differentiation at the cellular, tissue or organismal levels via regulation of numerous target genes. In part due to the incomplete inventory and functional accounting of Myc’s targets, no principle unifies Myc action. To relate the dynamics of Myc-binding with target expression and function in a system where Myc-levels are temporally and physiologically regulated, the transcriptomes and the genome-wide distributions of Myc, RNA polymerase II and chromatin modifications were compared during lymphocyte activation and in ES cells. A remarkably simple rule emerged from this quantitative analysis: Myc is not an on-off switch, but is a non-linear amplifier of expression, acting universally at active genes, except for immediate early genes that are strongly induced before Myc. This rule of Myc action explains the vast majority of Myc biology observed in literature.
2012-09-27 | GSE37222 | GEO