Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations
Abstract A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genom...
Saved in:
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Springer Nature
2022-09-01
|
| Series: | Molecular Systems Biology |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/msb.202210979 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849341784455380992 |
|---|---|
| author | Karun Kiani Eric M Sanford Yogesh Goyal Arjun Raj |
| author_facet | Karun Kiani Eric M Sanford Yogesh Goyal Arjun Raj |
| author_sort | Karun Kiani |
| collection | DOAJ |
| description | Abstract A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genome, which are thought to correspond to transcription factor‐binding events. In concert with RNA‐sequencing, these data in principle enable such mappings; however, few studies have looked at their concordance over short‐duration treatments with specific perturbations. Here, we used tandem, bulk ATAC‐seq, and RNA‐seq measurements from MCF‐7 breast carcinoma cells to systematically evaluate the concordance between changes in accessibility and changes in expression in response to retinoic acid and TGF‐β. We found two classes of genes whose expression showed a significant change: those that showed some changes in the accessibility of nearby chromatin, and those that showed virtually no change despite strong changes in expression. The peaks associated with genes in the former group had lower baseline accessibility prior to exposure to signal. Focusing the analysis specifically on peaks with motifs for transcription factors associated with retinoic acid and TGF‐β signaling did not reduce the lack of correspondence. Analysis of paired chromatin accessibility and gene expression data from distinct paths along the hematopoietic differentiation trajectory showed a much stronger correspondence, suggesting that the multifactorial biological processes associated with differentiation may lead to changes in chromatin accessibility that reflect rather than driving altered transcriptional status. Together, these results show many gene expression changes can happen independently of changes in the accessibility of local chromatin in the context of a single‐factor perturbation. |
| format | Article |
| id | doaj-art-65c7f98ab5a945fb99fbcef6dff68b02 |
| institution | Kabale University |
| issn | 1744-4292 |
| language | English |
| publishDate | 2022-09-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | Molecular Systems Biology |
| spelling | doaj-art-65c7f98ab5a945fb99fbcef6dff68b022025-08-20T03:43:34ZengSpringer NatureMolecular Systems Biology1744-42922022-09-0118911710.15252/msb.202210979Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbationsKarun Kiani0Eric M Sanford1Yogesh Goyal2Arjun Raj3Genetics and Epigenetics, Cell and Molecular Biology Graduate Group, Perelman School of Medicine, University of PennsylvaniaGenomics and Computational Biology Graduate Group, Perelman School of Medicine, University of PennsylvaniaDepartment of Bioengineering, School of Engineering and Applied Sciences, University of PennsylvaniaDepartment of Bioengineering, School of Engineering and Applied Sciences, University of PennsylvaniaAbstract A major goal in the field of transcriptional regulation is the mapping of changes in the binding of transcription factors to the resultant changes in gene expression. Recently, methods for measuring chromatin accessibility have enabled us to measure changes in accessibility across the genome, which are thought to correspond to transcription factor‐binding events. In concert with RNA‐sequencing, these data in principle enable such mappings; however, few studies have looked at their concordance over short‐duration treatments with specific perturbations. Here, we used tandem, bulk ATAC‐seq, and RNA‐seq measurements from MCF‐7 breast carcinoma cells to systematically evaluate the concordance between changes in accessibility and changes in expression in response to retinoic acid and TGF‐β. We found two classes of genes whose expression showed a significant change: those that showed some changes in the accessibility of nearby chromatin, and those that showed virtually no change despite strong changes in expression. The peaks associated with genes in the former group had lower baseline accessibility prior to exposure to signal. Focusing the analysis specifically on peaks with motifs for transcription factors associated with retinoic acid and TGF‐β signaling did not reduce the lack of correspondence. Analysis of paired chromatin accessibility and gene expression data from distinct paths along the hematopoietic differentiation trajectory showed a much stronger correspondence, suggesting that the multifactorial biological processes associated with differentiation may lead to changes in chromatin accessibility that reflect rather than driving altered transcriptional status. Together, these results show many gene expression changes can happen independently of changes in the accessibility of local chromatin in the context of a single‐factor perturbation.https://doi.org/10.15252/msb.202210979chromatin accessibilitygene regulationmulti‐omics integrationRNA‐seq and ATAC‐seq concordancesignal response |
| spellingShingle | Karun Kiani Eric M Sanford Yogesh Goyal Arjun Raj Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations Molecular Systems Biology chromatin accessibility gene regulation multi‐omics integration RNA‐seq and ATAC‐seq concordance signal response |
| title | Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations |
| title_full | Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations |
| title_fullStr | Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations |
| title_full_unstemmed | Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations |
| title_short | Changes in chromatin accessibility are not concordant with transcriptional changes for single‐factor perturbations |
| title_sort | changes in chromatin accessibility are not concordant with transcriptional changes for single factor perturbations |
| topic | chromatin accessibility gene regulation multi‐omics integration RNA‐seq and ATAC‐seq concordance signal response |
| url | https://doi.org/10.15252/msb.202210979 |
| work_keys_str_mv | AT karunkiani changesinchromatinaccessibilityarenotconcordantwithtranscriptionalchangesforsinglefactorperturbations AT ericmsanford changesinchromatinaccessibilityarenotconcordantwithtranscriptionalchangesforsinglefactorperturbations AT yogeshgoyal changesinchromatinaccessibilityarenotconcordantwithtranscriptionalchangesforsinglefactorperturbations AT arjunraj changesinchromatinaccessibilityarenotconcordantwithtranscriptionalchangesforsinglefactorperturbations |