Unit:
Κατεύθυνση Μοριακή και Εφαρμοσμένη ΦυσιολογίαLibrary of the School of Health Sciences
Supervisors info:
Επίκουρη Καθηγήτρια Πιπέρη Χριστίνα
Original Title:
Μελέτη της έκφρασης της H1x και H4K20me3 σε κυτταρικές σειρές γλοιωμάτων
Translated title:
Investigation of H1x expression and H4K20 trimethylation in brain tumor cell lines
Summary:
Gliomas are the commonest type of primary brain tumors, arising from
glial cells. Their degree of malignancy varies between well differentiated
tumors and high grade aggressive tumors which barely respond to current
therapeutic strategies, such as glioblastoma multiform. Environmental and
genetic factors have been associated with gliomagenesis. Currently epigenetic
modifications are being investigated for their contribution to gliomagenesis.
DNA of eukaryotes is packed in chromatin, which consists of nucleosomes,
146 base pairs of DNA wrapped around an octamer of histones (H2A, H2B, H3, H4)
and a linker histone (H1). Histones are responsible for the structure of
nucleosome and are implicated in replication and repair mechanisms of DNA, as
well as in gene expression. Histones are subjected to epigenetic modifications
post- translation, and therefore are considered to be implicated in
transcriptional alterations and development of a variety of diseases and
tumors, including gliomas.
In the present study, the expression of H1x, H3k9me3 and H4K20me3 was
investigated in normal brain tissue, as well as in glioma cell lines and human
astrocytic tumors with immunohistochemistry and Western blot analysis.
Furthermore, correlation with histopathologic features was explored. Results
indicate for the first time that deregulation of H1x expression is implicated
in the late stages of the glioma progression, possibly serving as a potential
biomarker. Furthermore, loss of H4K20me3 was associated with progression of
astrocytic tumors to more aggressive forms, while H3K9me3 plays a secondary
role. In conclusion, there is evidence that epigenetic modifications of
chromatin participate in glioma pathogenesis and need future studies.
Keywords:
Brain tumor cell lines, Histone modifications Η4Κ20me3 H3K9me3, H1x, Astrocytic tumors, Epigenetics
Number of references:
107
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