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Series GSE98551 Query DataSets for GSE98551
Status Public on May 23, 2017
Title Chromatin structure and CTCF across the MCF10 breast cancer progression series (ChIP-Seq)
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary Transcription and processing of histone mRNAs occurs at subnuclear domains known as Histone Locus Bodies (HLBs). Although it is known that higher-order chromatin organization is dysregulated in cancer, structural alterations within HLB across breast cancer progression are unclear. Differential expression across known as MCF10, a basal triple negative breast cancer progression model, followed by pathway analysis demonstrated many alterations in signaling cascades known to be related to proliferation. Positional gene enrichment identified the hist1 gene locus at chromosome 6p22 as the most significantly altered cluster of genes from the normal-like MCF10A to premalignant MCF10AT1. The malignant MCF10CA1a had a more varied expression pattern across the hist1 locus. Within this region there are three subclusters of hist1 genes which were generally upregulated while intervening genes were more frequently downregulated. Extending these findings to TCGA breast tumors revealed that normal adjacent tissue had lower expression within the subclusters than their matched tumor samples. Moreover, the expression pattern within the hist1 locus comparing normal versus tumors recapitulated a very similar pattern to that comparing 10A to AT1 or CA1a. Since the hist1 locus is transcribed and processed at a specific subnuclear microenvironment, the higher order chromatin organization of this locus may be a critical component of its regulation. We addressed whether CTCF, a key chromatin organizing protein, may play a role in organizing the hist1 HLB. Immunofluorescence for CTCF along with NPAT, a protein which decorates this locus, identified that CTCF may tether the hist1 HLB to the nuclear matrix. All three subclusters reside within a single topologically associating domain wherein interacting loops are bound by CTCF. Inter-subcluster interactions are lost in the premalignant AT1. Consistent with the varied expression across the hist1 HLB in CA1a, inter-subcluster interactions are regained in the malignant state. These data suggest a transient state in highly proliferative breast cancer cells in which the hist1 HLB is dynamically reorganized.
Overall design CTCF ChIP-Seq
Contributor(s) Fritz A, Boyd J, Tye C, Lian J, Stein G
Citation(s) 28504305
NIH grant(s)
Grant ID Grant title Affiliation Name
R01 CA139322 Cell Cycle Regulation of Histone Gene Expression UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE Gary S. Stein
P01 CA082834 Nuclear Structure and Gene Expression UNIVERSITY OF VERMONT AND STATE AGRICULTURAL COLLEGE Janet L Stein
Submission date May 04, 2017
Last update date Nov 07, 2023
Contact name Jonathan AR Gordon
Organization name University of Vermont
Department Biochemistry
Street address 89 Beaumont Ave Given E209
City Burlington
State/province VT
ZIP/Postal code 05405
Country USA
Platforms (1)
GPL18460 Illumina HiSeq 1500 (Homo sapiens)
Samples (9)
GSM2599084 MCF10A CTCF ChIPseq Rep1
GSM2599085 MCF10A CTCF ChIPseq Rep2
GSM2599086 MCF10AT1 CTCF ChIPseq Rep1
BioProject PRJNA385492
SRA SRP106469

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Supplementary file Size Download File type/resource 899.8 Mb (ftp)(http) BW
GSE98551_MCF10AT1_CTCF_pooled_peaks_passIDR.05.narrowPeak.gz 1.0 Mb (ftp)(http) NARROWPEAK 919.8 Mb (ftp)(http) BW
GSE98551_MCF10A_CTCF_pooled_peaks_passIDR.05.narrowPeak.gz 1.2 Mb (ftp)(http) NARROWPEAK 992.4 Mb (ftp)(http) BW
GSE98551_MCF10CA1_CTCF_pooled_peaks_passIDR.05.narrowPeak.gz 1.0 Mb (ftp)(http) NARROWPEAK
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