Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer
Epigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell...
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doaj-220b3fb9a3004f02813fecead72842142020-11-25T01:57:17ZengMDPI AGCancers2072-66942019-08-01118114210.3390/cancers11081142cancers11081142Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal CancerHannah Flebbe0Feda H. Hamdan1Vijayalakshmi Kari2Julia Kitz3Jochen Gaedcke4B. Michael Ghadimi5Steven A. Johnsen6Marian Grade7Department of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyInstitute of Pathology, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyDepartment of General, Visceral and Pediatric Surgery, University Medical Center Goettingen, 37075 Goettingen, GermanyEpigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell lines, only limited data are available from primary tumors. We therefore examined whether cancer-specific alterations in H3K27ac occupancy can be identified in primary rectal cancer. Tissue samples from primary rectal cancer and matched mucosa were obtained. ChIP-seq for H3K27ac was performed and differentially occupied regions were identified. The expression of selected genes displaying differential occupancy between tumor and mucosa were examined in gene expression data from an independent patient cohort. Differential expression of four proteins was further examined by immunohistochemistry. ChIP-seq for H3K27ac in primary rectal cancer and matched mucosa was successfully performed and revealed differential binding on 44 regions. This led to the identification of genes with increased H3K27ac, i.e., <i>RIPK2</i>, <i>FOXQ1</i>, <i>KRT23</i>, and <i>EPHX4</i>, which were also highly upregulated in primary rectal cancer in an independent dataset. The increased expression of these four proteins was confirmed by immunohistochemistry. This study demonstrates the feasibility of ChIP-seq-based epigenome mapping of primary rectal cancer and confirms the value of H3K27ac occupancy to predict gene expression differences.https://www.mdpi.com/2072-6694/11/8/1142ChIP-seqchromatinepigeneticshistone modificationH3K27acrectal cancergene expression |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hannah Flebbe Feda H. Hamdan Vijayalakshmi Kari Julia Kitz Jochen Gaedcke B. Michael Ghadimi Steven A. Johnsen Marian Grade |
spellingShingle |
Hannah Flebbe Feda H. Hamdan Vijayalakshmi Kari Julia Kitz Jochen Gaedcke B. Michael Ghadimi Steven A. Johnsen Marian Grade Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer Cancers ChIP-seq chromatin epigenetics histone modification H3K27ac rectal cancer gene expression |
author_facet |
Hannah Flebbe Feda H. Hamdan Vijayalakshmi Kari Julia Kitz Jochen Gaedcke B. Michael Ghadimi Steven A. Johnsen Marian Grade |
author_sort |
Hannah Flebbe |
title |
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer |
title_short |
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer |
title_full |
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer |
title_fullStr |
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer |
title_full_unstemmed |
Epigenome Mapping Identifies Tumor-Specific Gene Expression in Primary Rectal Cancer |
title_sort |
epigenome mapping identifies tumor-specific gene expression in primary rectal cancer |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-08-01 |
description |
Epigenetic alterations play a central role in cancer development and progression. The acetylation of histone 3 at lysine 27 (H3K27ac) specifically marks active genes. While chromatin immunoprecipitation (ChIP) followed by next-generation sequencing (ChIP-seq) analyses are commonly performed in cell lines, only limited data are available from primary tumors. We therefore examined whether cancer-specific alterations in H3K27ac occupancy can be identified in primary rectal cancer. Tissue samples from primary rectal cancer and matched mucosa were obtained. ChIP-seq for H3K27ac was performed and differentially occupied regions were identified. The expression of selected genes displaying differential occupancy between tumor and mucosa were examined in gene expression data from an independent patient cohort. Differential expression of four proteins was further examined by immunohistochemistry. ChIP-seq for H3K27ac in primary rectal cancer and matched mucosa was successfully performed and revealed differential binding on 44 regions. This led to the identification of genes with increased H3K27ac, i.e., <i>RIPK2</i>, <i>FOXQ1</i>, <i>KRT23</i>, and <i>EPHX4</i>, which were also highly upregulated in primary rectal cancer in an independent dataset. The increased expression of these four proteins was confirmed by immunohistochemistry. This study demonstrates the feasibility of ChIP-seq-based epigenome mapping of primary rectal cancer and confirms the value of H3K27ac occupancy to predict gene expression differences. |
topic |
ChIP-seq chromatin epigenetics histone modification H3K27ac rectal cancer gene expression |
url |
https://www.mdpi.com/2072-6694/11/8/1142 |
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