Histone H3 is aberrantly phosphorylated in glutamine-repeat diseases.
Double-labeling immunohistochemical studies staining with anti-ubiquitin and anti-phosphoserine antibodies and application of an enzymatic dephosphorylation technique reveal neuronal inclusions and affected nuclei to be aberrantly phosphorylated in brain tissues with patients with glutamine-repeat diseases. Regional distribution of the phosphorylated nuclei in neurons correlates with the pathology. To identify the target nuclear protein, transient expression of Huntington's disease exon 1 gene containing an expanded glutamine repeat was generated in a cell culture and nuclear inclusions were isolated with a fluorescence-activated cell sorting system. Immunoblotting studies of the aggregated nuclear proteins using anti-phosphoserine antibody demonstrate the protein of the aberrant phosphorylation as histone H3. The immunoblots of control and diseased brain tissues demonstrate that the phosphorylation of histone H3 is commonly increased in the diseased brains. Aberrant phosphorylation of histone H3 is surmised to be a shared pathological process in glutamine-repeat diseases.
Yazawa
Ikuru
I
Department of Neurology, Toranomon Hospital, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan. ikuru@toranomon.gr.jp
Hazeki
Noriko
N
Nakase
Hirofumi
H
Kanazawa
Ichiro
I
Tanaka
Masumi
M
D000328:Adult; D000368:Aged; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism*; D020271:Heredodegenerative Disorders, Nervous System / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010766:Phosphorylation
D006657:Histones; D005973:Glutamine