Related Experiment Video
Updated: Jun 24, 2025
An Integrated Platform for Genome-wide Mapping of Chromatin States Using High-throughput ChIP-sequencing in Tumor Tissues
Published on: April 5, 2018
Defining the heterogeneous molecular landscape of lung cancer cell responses to epigenetic inhibition
Chuwei Lin1, Catherine M Sniezek1, Christopher D McGann1
1Genome Sciences, University of Washington, Seattle, WA 98105, USA.
Abstract:
Epigenetic inhibitors exhibit powerful antiproliferative and anticancer activities. However, cellular responses to small-molecule epigenetic inhibition are heterogenous and dependent on factors such as the genetic background, metabolic state, and on-/off-target engagement of individual small-molecule compounds. The molecular study of the extent of this heterogeneity often measures changes in a single cell line or using a small number of compounds. To more comprehensively profile the effects of small-molecule perturbations and their influence on these heterogeneous cellular responses, we present a molecular resource based on the quantification of chromatin, proteome, and transcriptome remodeling due to histone deacetylase inhibitors (HDACi) in non-isogenic cell lines. Through quantitative molecular profiling of 10,621 proteins, these data reveal coordinated molecular remodeling of HDACi treated cancer cells. HDACi-regulated proteins differ greatly across cell lines with consistent (JUN, MAP2K3, CDKN1A) and divergent (CCND3, ASF1B, BRD7) cell-state effectors. Together these data provide valuable insight into cell-type driven and heterogeneous responses that must be taken into consideration when monitoring molecular perturbations in culture models.
Insights
Small-molecule epigenetic inhibitors show anticancer effects, but responses vary. This study quantifies chromatin, proteome, and transcriptome changes in cancer cells treated with histone deacetylase inhibitors (HDACi) to map this heterogeneity.
Area of Science:
- Molecular Biology
- Cancer Research
- Epigenetics
Background:
- Epigenetic inhibitors possess potent antiproliferative and anticancer properties.
- Cellular responses to small-molecule epigenetic inhibition are highly heterogeneous.
- This heterogeneity is influenced by genetic background, metabolic state, and compound specificity.
Purpose of the Study:
- To comprehensively profile the effects of small-molecule perturbations on heterogeneous cellular responses.
- To create a molecular resource for studying chromatin, proteome, and transcriptome remodeling.
- To investigate the impact of histone deacetylase inhibitors (HDACi) in non-isogenic cell lines.
Main Methods:
- Quantitative molecular profiling of 10,621 proteins in HDACi-treated cancer cells.
- Analysis of chromatin, proteome, and transcriptome remodeling.
- Utilizing non-isogenic cell lines to assess heterogeneity.
Main Results:
- HDACi treatment induced coordinated molecular remodeling in cancer cells.
- HDACi-regulated proteins exhibited significant differences across cell lines.
- Identified consistent (JUN, MAP2K3, CDKN1A) and divergent (CCND3, ASF1B, BRD7) cell-state effectors.
Conclusions:
- The study provides valuable insights into cell-type driven and heterogeneous responses to epigenetic perturbations.
- Understanding this heterogeneity is crucial for interpreting molecular perturbations in culture models.
- This resource aids in comprehending the nuanced effects of HDAC inhibitors in cancer research.
More Related Videos
Related Concept Videos
01:37Epigenetic Regulation
X-chromosome...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...