Hyperacetylation in prostate cancer induces cell cycle aberrations, chromatin reorganization and altered gene expression profiles.
Histone acetylation is a fundamental mechanism in the regulation of local chromatin conformation and gene expression. Research has focused on the impact of altered epigenetic environments on the expression of specific genes and their pathways. However, changes in histone acetylation also have a global impact on the cell. In this study we used digital texture analysis to assess global chromatin patterns following treatment with trichostatin A (TSA) and have observed significant alterations in the condensation and distribution of higher-order chromatin, which were associated with altered gene expression profiles in both immortalised normal PNT1A prostate cell line and androgen-dependent prostate cancer cell line LNCaP. Furthermore, the extent of TSA-induced disruption was both cell cycle and cell line dependent. This was illustrated by the identification of sub-populations of prostate cancer cells expressing high levels of H3K9 acetylation in the G(2)/M phase of the cell cycle that were absent in normal cell populations. In addition, the analysis of enriched populations of G(1) cells showed a global decondensation of chromatin exclusively in normal cells.
Watson
Jenny A
JA
Centre for Cancer Research and Cell Biology, Queen's University Belfast, Northern Ireland. jennywatson2008@gmail.com
McKenna
Declan J
DJ
Maxwell
Perry
P
Diamond
James
J
Arthur
Ken
K
McKelvey-Martin
Valerie J
VJ
Hamilton
Peter W
PW
D000107:Acetylation / Q000187:drug effects; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002843:Chromatin / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D008239:Lysine / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology*
D002843:Chromatin; D006657:Histones; D006877:Hydroxamic Acids; C012589:trichostatin A; D008239:Lysine