Heterochromatin marks HP1gamma, HP1alpha and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours

0347140 - ÚMG 2012 RIV GB eng J - Journal Article
Bartkova, J. - Moudrý, Pavel - Hodný, Zdeněk - Lukas, J. - Rajpert-De Meyts, E. - Bártek, Jiří
Heterochromatin marks HP1gamma, HP1alpha and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours.
International Journal of Andrology. Roč. 34, 4 Pt 2 (2011), e103-e113. ISSN 0105-6263
R&D Projects: GA ČR GA301/08/0353
Grant - others:Lundbeck Foundation(DK) R13-A1287; EU FP7(XE) TRIREME 223575
Institutional research plan: CEZ:AV0Z50520514
Keywords : heterochromatinization * DNA damage response * germinal tumours
Subject RIV: EB - Genetics ; Molecular Biology
Impact factor: 3.591, year: 2011

Heterochromatinization has been implicated in fundamental biological and pathological processes including differentiation, senescence, ageing and tumorigenesis; however, little is known about its regulation and roles in human cells and tissues in vivo. Here, we show distinct cell-type- and cancer-stage-associated patterns of key heterochromatin marks: histone H3 trimethylated at lysine 9 (H3K9me3) and heterochromatic adaptor proteins HP1α and HP1γ, compared with the γH2AX marker of endogenously activated DNA damage response (DDR) and proliferation markers in normal human foetal and adult testes, pre-invasive carcinoma in situ (CIS) lesions and a series of overt germ cell tumours, including seminomas, embryonal carcinomas and teratomas. Among striking findings were high levels of HP1γ in foetal gonocytes, CIS and seminomas; enhanced multimarker heterochromatinization without DDR activation in CIS; and enhanced HP1α in teratoma structures with epithelial and neuronal differentiation.
Permanent Link: http://hdl.handle.net/11104/0187984