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Series GSE105786 Query DataSets for GSE105786
Status Public on Apr 04, 2019
Title MTHFD1 links folate metabolism to BRD4-mediated transcriptional regulation
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary The histone acetyl-reader BRD4 is an important regulator of chromatin structure and transcription, yet factors modulating its activity have remained elusive. Here we describe two complementary screens for functional regulators and physical interactors of BRD4, which converge on the folate pathway enzyme MTHFD1. We show that a fraction of MTHFD1 resides in the nucleus, where it is recruited to distinct genomic loci by direct interaction with BRD4. Inhibition of either BRD4 or MTHFD1 results in similar changes in nuclear metabolite composition and gene expression, and pharmacologic inhibitors of the two pathways synergize to impair cancer cell viability in vitro and in vivo. Our finding that MTHFD1 and other metabolic enzymes are chromatin-associated suggests a direct role for nuclear metabolism in the control of gene expression.
Overall design 35 ChIP-seq samples for BRD4, MTHFD1 and H3K27ac were produced, along with the respective IgG controls in HAP1 cells treated with dBET6 or DMSO. 93 RNA-seq samples for WT, MTHFD1KO or treated cell were produced.
Contributor(s) Sdelci S, Rendeiro AF, Rathert P, Hofstätter G, Ringler A, Moll HP, You W, Klavins K, Gürtl B, Farlik M, Schick S, Klepsch F, Oldach M, Buphamalai P, Schischlik F, Májek P, Parapatics K, Schmidl C, Schuster M, Penz T, Buckley DL, Hudecz O, Imre R, Kralovics R, Bennett KL, Müller A, Mechtler K, Menche J, Bradner JE, Winter GE, Casanova E, Bock C, Zuber J, Kubicek S
Citation(s) 31133746
Submission date Oct 23, 2017
Last update date Jul 04, 2019
Contact name Christoph Bock
Organization name CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences
Street address Lazarettgasse 14
City Vienna
ZIP/Postal code 1090
Country Austria
Platforms (2)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
GPL21290 Illumina HiSeq 3000 (Homo sapiens)
Samples (128)
GSM2828225 ChIP-seq for BRD4 in HAP1 cell line treated with dBET6, replicate 1
GSM2828226 ChIP-seq for BRD4 in HAP1 cell line treated with dBET6, replicate 2
GSM2828227 ChIP-seq for BRD4 in HAP1 cell line treated with DMSO, replicate 1
BioProject PRJNA415413
SRA SRP120974

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SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE105786_RAW.tar 9.8 Gb (http)(custom) TAR (of BIGWIG)
GSE105786_cuffnorm.genes.fpkm_table.tsv.gz 11.3 Mb (ftp)(http) TSV
GSE105786_cuffnorm.genes.fpkm_table2_GSM3573307-GSM3573315.tsv.gz 267.1 Kb (ftp)(http) TSV
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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