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Series GSE92882 Query DataSets for GSE92882
Status Public on Mar 29, 2017
Title Functional genomic analysis of the haploinsufficient tumor suppressor, CUX1
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Expression profiling by high throughput sequencing
Summary CUX1 is a homeodomain-containing transcription factor that is conserved, ubiquitous, and essential in vertebrates and invertebrates. CUX1 is mutated or deleted in high-risk myeloid neoplasms and solid tumors, resulting in haploinsufficiency and tumor growth. Here we provide the first analysis of endogenous, whole genome, CUX1 DNA binding. We demonstrate that CUX1 binds with transcriptional activators and cohesin at distal enhancers across three different human cell types. Haploinsufficiency of CUX1 altered the expression of a large number of genes, including cell cycle regulators, with concomitant increased cellular proliferation. Surprisingly, CUX1 occupancy decreased genome-wide in the haploinsufficient state, and binding site affinity did not correlate with differential gene expression. Instead, differentially expressed genes had multiple, low-affinity CUX1 binding sites, consistent with an analog model for CUX1 gene regulation. A machine-learning algorithm determined that chromatin accessibility, enhancer activity, and distance to the transcription start site are features of functional CUX1 DNA binding. Moreover, CUX1 is enriched at sites of DNA looping, and these loops connect CUX1 to the promoters of target genes. We propose that CUX1 is an analog transcription factor that regulates target genes through higher order genome architecture.
Overall design RNA-seq and ChIP-seq of CUX1 in the wildtype and haploinsufficient states in K562 cells
Contributor(s) McNerney M
Citation(s) 28369554
NIH grant(s)
Grant ID Grant title Affiliation Name
K08 CA181254 Determining the role of CUX1 in myeloid neoplasia UNIVERSITY OF CHICAGO Megan Elizabeth McNerney
Submission date Dec 23, 2016
Last update date May 15, 2019
Contact name Megan E. McNerney
Phone 7738348896
Organization name The University of Chicago
Department Pathology
Lab Megan McNerney
Street address 900 East 57th Street, KCBD 5128
City Chicago
State/province Illinois
ZIP/Postal code 60637
Country USA
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL20301 Illumina HiSeq 4000 (Homo sapiens)
Samples (17)
GSM2439233 input.rep1_ChIP-seq
GSM2439234 shCUX1-A.rep1_ChIP-seq
GSM2439235 shCUX1-B.rep1_ChIP-seq
BioProject PRJNA358710
SRA SRP095607

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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE92882_DiffBindResults.txt.gz 82.5 Kb (ftp)(http) TXT
GSE92882_EdgeRResults.txt.gz 397.2 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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