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Series GSE205758 Query DataSets for GSE205758
Status Public on Sep 07, 2022
Title Multimerization of MYC shields stalled replication forks from RNA polymerase [CUT&RUN, ChIP-seq]
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Oncoproteins of the MYC family drive the development of numerous human tumors. In unperturbed cells, MYC proteins bind to virtually all active promoters and control transcription by RNA Polymerase II (RNAPII). MYC proteins can also coordinate transcription with DNA replication and promote the repair of transcription-associated DNA damage, but how they exert these mechanistically diverse functions is unknown. Here we show that MYC dissociates from many of its binding sites in active promoters and forms multimeric, often sphere-like structures in response to perturbation of transcription elongation, mRNA splicing or inhibition of the proteasome. Multimerization is accompanied by a global change in the MYC interactome towards proteins involved in transcription termination and RNA processing. MYC multimers accumulate on chromatin immediately adjacent to stalled replication forks and surround FANCD2, ATR and BRCA1 proteins, which are located at stalled forks. MYC multimerization is triggered in a HUWE1 and ubiquitylation-dependent manner. At active promoters, MYC multimers block antisense transcription and stabilize FANCD2 association with chromatin. This limits DNA double-strand break formation during S-phase and allows rapid recovery from replication stress, suggesting that multimerization of MYC enables tumor cells to proliferate under stressful conditions
Overall design Chromatin binding of MYC, FANCD2, ATR, SPT5, RNAPII, pS4S8RPA, MAX, JUN and EXOSC10 along with gene expression data after variation chemical treatments
Contributor(s) Solvie D, Baluapuri A, Uhl L, Endres T, Wolf E, Eilers M
Citation(s) 36424410
Submission date Jun 09, 2022
Last update date Dec 02, 2022
Contact name Martin Eilers
Organization name University of Wuerzburg
Department Chair for Biochemistry and Molecular Biology
Lab Martin Eilers
Street address Am Hubland
City Wuerzburg
ZIP/Postal code 97074
Country Germany
Platforms (2)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
GPL30173 NextSeq 2000 (Homo sapiens)
Samples (59)
GSM6222800 ChIP-seq Exp66 Input merge
GSM6222801 ChIP-seq Exp66 MYC H2O rep1
GSM6222802 ChIP-seq Exp66 MYC HU rep1
This SubSeries is part of SuperSeries:
GSE205585 Multimerization of MYC shields stalled replication forks from RNA polymerase.
BioProject PRJNA847458

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Supplementary file Size Download File type/resource
GSE205758_RAW.tar 7.5 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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