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Heterochromatin marks HP1γ, HP1α and H3K9me3, and DNA damage response activation in human testis development and germ cell tumours.
MedLine Citation:
PMID:  20695923     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Heterochromatinization has been implicated in fundamental biological and pathological processes including differentiation, senescence, ageing and tumourigenesis; 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 (n = 4) and adult (n = 29) testes, pre-invasive carcinoma in situ (CIS; n = 26) lesions and a series of overt germ cell tumours, including seminomas (n = 26), embryonal carcinomas (n = 18) and teratomas (n = 11). 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. Differential expression of the three heterochromatin markers suggests their partly non-overlapping roles, and separation of heterochromatinization from DDR activation highlights distinct responses of germ cells vs. somatic tissues in early tumourigenesis. Conceptually interesting findings were that subsets of human cells in vivo proliferate despite enhanced heterochromatinization, and that cells can strongly express even multiple heterochromatin features in the absence of functional retinoblastoma protein and without DDR activation. Overall, these results provide novel insights into cell-related and tumour-related diversity of heterochromatin in human tissues in vivo, relevant for andrology and intrinsic anti-tumour defence roles attributed to activated DDR and cellular senescence.
Authors:
J Bartkova; P Moudry; Z Hodny; J Lukas; E Rajpert-De Meyts; J Bartek
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Publication Detail:
Type:  Journal Article     Date:  2010-08-01
Journal Detail:
Title:  International journal of andrology     Volume:  34     ISSN:  1365-2605     ISO Abbreviation:  Int. J. Androl.     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-07-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8000141     Medline TA:  Int J Androl     Country:  England    
Other Details:
Languages:  eng     Pagination:  e103-13     Citation Subset:  IM    
Copyright Information:
© 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.
Affiliation:
Institute of Cancer Biology and Centre for Genotoxic Stress Research, Danish Cancer Society, Copenhagen, Denmark Department of Genome Integrity, Institute of Molecular Genetics, Academy of Sciences of the Czech Republic, Prague, Czech Republic University Department of Growth and Reproduction, Rigshospitalet, Copenhagen, Denmark.
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