Histone H1x is highly expressed in human neuroendocrine cells and tumours.
BACKGROUND
Histone H1x is a ubiquitously expressed member of the H1 histone family. H1 histones, also called linker histones, stabilize compact, higher order structures of chromatin. In addition to their role as structural proteins, they actively regulate gene expression and participate in chromatin-based processes like DNA replication and repair. The epigenetic contribution of H1 histones to these mechanisms makes it conceivable that they also take part in malignant transformation.


METHODS
Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study.


RESULTS
We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues.


CONCLUSIONS
We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate.
Warneboldt
Julia
J
Institute for Biochemistry and Molecular Cell Biology, University of Göttingen, Humboldtallee 23, D-37073 Göttingen, Germany. jwarneb@gwdg.de
Haller
Florian
F
Horstmann
Olaf
O
Danner
Bernhard C
BC
Füzesi
László
L
Doenecke
Detlef
D
Happel
Nicole
N
D015153:Blotting, Western; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism* / Q000473:pathology; D053379:Chromogranin A; D004268:DNA-Binding Proteins; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D015723:Gene Library; D006801:Humans; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D055099:Neuroendocrine Cells / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D016601:RNA-Binding Proteins; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016324:Sequence Tagged Sites
D053379:Chromogranin A; D004268:DNA-Binding Proteins; C525594:H1-10 protein, human; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins