|
| Status |
Public on May 31, 2019 |
| Title |
Matrix stiffness induces a tumorigenic phenotype in mammary epithelium through changes in chromatin accessibility |
| Organism |
Homo sapiens |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| Summary |
In breast cancer, the increased stiffness of the extracellular matrix (ECM) is a key driver of malignancy. Yet little is known about the epigenomic changes that underlie the tumorigenic impact of ECM mechanics. Here, we show in a 3D culture model of breast cancer that stiff ECM induces a tumorigenic phenotype through changes in chromatin state. We found that increased stiffness yielded cells with more wrinkled nuclei and with increased lamina-associated chromatin, that cells cultured in stiff matrices displayed more accessible chromatin sites, which exhibited footprints of Sp1 binding, and that Sp1 acts along with histone deacetylases (HDAC) 3 and 8 to regulate the induction of stiffness-mediated tumorigenicity. Just as cell culture on soft environments or in them rather than on tissue-culture plastic better recapitulates the acinar morphology observed in mammary epithelium in vivo, mammary epithelial cells cultured on soft microenvironments or in them also more closely replicate the in vivo chromatin state. Our results emphasize the importance of culture conditions for epigenomic studies, and reveal that chromatin state is a critical mediator of mechanotransduction.
|
| |
|
| Overall design |
Examination of chromatin accessibility profiles of mammary epithelial cells in hydrogel culture of different stiffness
|
| |
|
| Contributor(s) |
Stowers R, Shcherbina A, Israeli J, Gruber J, Chang J, Nam S, Rabiee A, Teruel M, Snyder M, Kundaje A, Chaudhuri O |
| Citation(s) |
31285581 |
| |
| Submission date |
May 30, 2019 |
| Last update date |
Aug 30, 2019 |
| Contact name |
Carlos Aguilar |
| E-mail(s) |
caguilar@umich.edu
|
| Organization name |
University of Michigan - Ann Arbor
|
| Department |
Dept. of Biomedical Engineering & Biointerfaces Institute
|
| Lab |
NANO-OMIC-BIO-ENGINEERING-LAB
|
| Street address |
300 Pasteur Dr
|
| City |
Ann Arbor |
| State/province |
MI |
| ZIP/Postal code |
48109 |
| Country |
USA |
| |
|
| Platforms (2) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
|
| Samples (20)
|
|
| Relations |
| BioProject |
PRJNA545478 |
| SRA |
SRP199869 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE131968_100Pa_1_TAAGGCGA_1_pf.PE2SE.nodup.tn5_pooled.pf.pval.signal.bigwig |
1.0 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_100Pa_1_TAAGGCGA_1_pf.merged.nodup.tn5.pooled.fc.signal.bigwig |
1.5 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_100Pa_3D_ppr.IDR0.1.filt.narrowPeak.gz |
812.3 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_100Pa_3D_ppr.naive_overlap.filt.narrowPeak.gz |
2.0 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_100Pa_saha_1_TAAGGCGA_R1.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig |
1021.6 Mb |
(ftp)(http) |
BIGWIG |
| GSE131968_100Pa_saha_1_TAAGGCGA_R1.PE2SE.nodup.tn5_pooled.pf.pval.signal.bigwig |
830.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE131968_2000Pa_1_TCCTGAGC_1_pf.nodup.tn5_pooled.pf.fc.signal.bigwig |
1.1 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_2000Pa_1_TCCTGAGC_1_pf.nodup.tn5_pooled.pf.pval.signal.bigwig |
848.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE131968_2000Pa_3D_ppr.IDR0.1.filt.narrowPeak.gz |
728.6 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_2000Pa_3D_ppr.naive_overlap.filt.narrowPeak.gz |
1.6 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_2000Pa_saha_1_TCCTGAGC_R1.PE2SE.nodup.tn5_pooled.pf.pval.signal.bigwig |
1.3 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_2000Pa_saha_1_TCCTGAGC_R1.merged.nodup.tn5.pooled.fc.signal.bigwig |
1.6 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_2D_Soft_CAGAGAGG_R1.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig |
1.5 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_2D_Soft_CAGAGAGG_R1.PE2SE.nodup.tn5_pooled.pf.pval.signal.bigwig |
1.2 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_2D_TCPS_1_CAGAGAGG_R1.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig |
476.9 Mb |
(ftp)(http) |
BIGWIG |
| GSE131968_2D_TCPS_1_CAGAGAGG_R1.PE2SE.nodup.tn5_pooled.pf.pval.signal.bigwig |
342.0 Mb |
(ftp)(http) |
BIGWIG |
| GSE131968_2D_TCPS_ppr.IDR0.1.filt.narrowPeak.gz |
683.8 Kb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_2D_TCPS_ppr.naive_overlap.filt.narrowPeak.gz |
1.5 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_2D_soft_ppr.IDR0.1.filt.narrowPeak.gz |
2.3 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_2D_soft_ppr.naive_overlap.filt.narrowPeak.gz |
4.1 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_atac_mamgland_ppr.IDR0.1.filt.narrowPeak.gz |
2.1 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_atac_mamgland_ppr.naive_overlap.filt.narrowPeak.gz |
3.7 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_mamgland_1_ENCFF488ELU.PE2SE.nodup.tn5_pooled.pf.fc.signal.bigwig |
1.8 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_mamgland_rep1_1_ENCFF488ELU.merged.nodup.tn5.pooled.pval.signal.bigwig |
1.6 Gb |
(ftp)(http) |
BIGWIG |
| GSE131968_saha_100Pa_ppr.IDR0.1.filt.narrowPeak.gz |
1.7 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_saha_100Pa_ppr.naive_overlap.filt.narrowPeak.gz |
3.3 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_saha_2000Pa_ppr.IDR0.1.filt.narrowPeak.gz |
1.7 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_saha_2000Pa_ppr.naive_overlap.filt.narrowPeak.gz |
3.6 Mb |
(ftp)(http) |
NARROWPEAK |
| GSE131968_tagAlign.counts.for.naive.overlap.merged.peaks.txt.gz |
1.7 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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