Abstract
BackgroundHistone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. However, our knowledge of PTM patterns in human tumours is limited.MethodsMS-based analyses were used to quantify global alterations of histone PTMs in colorectal cancer (CRC) samples. Histones isolated from 12 CRCs and their corresponding normal mucosa by acidic extraction were separated by SDS-PAGE and analysed by liquid chromatography-mass spectrometry.ResultsAmong 96 modified peptides, 41 distinct PTM sites were identified, of which 7, 13, 11, and 10 were located within the H2A, H2B, H3, and H4 sequences, respectively, and distributed among the amino-terminal tails and the globular domain of the four histones. Modification intensities were quantified for 33 sites, of which 4 showed significant (p-value ≤ 0.05) differences between CRC tissues and healthy mucosa samples. We identified histone H3 lysine 27 acetylation (H3K27Ac) as a modification upregulated in CRC, which had not been shown previously.ConclusionsThe present results indicate the usefulness of a bottom-up proteomic approach for the detection of histone modifications at a global scale. The differential abundance of H3K27Ac mark in CRC, a PTM associated with active enhancers, suggests its role in regulating genes whose expression changes in CRC.
Highlights
Histone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression
Most Colorectal cancer (CRC) are sporadic, and only a small proportion is associated with hereditary disorders with high penetration, such as Lynch syndrome, familial adenomatous polyposis and other polyposis syndromes mediated by rare germline mutations in DNA mismatch-repair genes and in the adenomatous polyposis coli (APC) gene [2]
Histones were isolated from 12 CRC tissues and corresponding normal mucosa, and equal protein amounts were separated by SDS-PAGE and subjected to qualitative LC-mass spectrometry (MS)/MS and quantitative label-free LC-MS analyses (Figure 1)
Summary
Histone post-translational modifications (PTMs) play an important role in the regulation of the expression of genes, including those involved in cancer development and progression. Our knowledge of PTM patterns in human tumours is limited. Colorectal cancer (CRC) is the most common cancer in the Polish population, and the leading cause of cancerrelated morbidity and mortality [1]. Histone post-translational modifications (PTMs) include lysine acetylation, arginine and lysine methylation, phosphorylation, proline isomerization, ubiquitination (Ub), ADP ribosylation, arginine citrullination, SUMOylation, carbonylation and biotinylation [6]. The most common PTMs are acetylation and methylation [7]. Despite the key role of epigenetic alterations in cancer development, little is known about the patterns of histone PTM alterations in human tumours [9]
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