title: The linker histone H1C contributes to the SCA7 nuclear phenotype.
abstract: Spinocerebellar ataxia type 7 (SCA7) is a neurodegenerative disease caused by a polyglutamine expansion in ataxin-7, a subunit of the SAGA coactivator, which leads to progressive neuronal dysfunction and cell death in cerebellum, brainstem and retina. Increased nuclear volume, chromatin decondensation and deregulated gene expression were reported in a SCA7 mouse model expressing mutant ataxin-7 in rod photoreceptors. We analyzed the SCA7-induced chromatin reorganization by immunogold labeling, stereology, electron tomography and showed that in SCA7 rods the most external heterochromatin ring, corresponding to facultative heterochromatin, becomes fragmented and decondensed. The amounts of acetylated histone H3 and H4 tails were found to be unchanged in nuclear extracts of SCA7 retinas and their cellular distribution appeared similar in wild-type and SCA7 mice in so far that in both cases acetylated histones are positioned at the interface between eu- and hetero-chromatin. We found that the amount of the linker histone H1c is strongly reduced in nuclear extracts of SCA7 retinas and that the cellular distribution of H1c is particularly altered in the facultative heterochromatin compartment. The decreased histone H1c content thus provides a coherent explanation for the chromatin decondensation observed in SCA7 rod photoreceptor nuclei.
authors.affiliation: Department of Structural Biology and Genomics, IGBMC (Institut de Génétique et de Biologie Moléculaire et Cellulaire) INSERM, U964, CNRS, UMR7104 1, rue Laurent Fries, BP10142 67404 Illkirch, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Kizilyaprak
authors.forename: Danièle
authors.initials: D
authors.lastname: Spehner
authors.forename: Didier
authors.initials: D
authors.lastname: Devys
authors.forename: Patrick
authors.initials: P
authors.lastname: Schultz
mesh_terms: D000107:Acetylation; D000818:Animals; D000067719:Ataxin-7; D002467:Cell Nucleus / Q000378:metabolism* / Q000648:ultrastructure; D002843:Chromatin / Q000378:metabolism; D006657:Histones / Q000032:analysis / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000067719:Ataxin-7; C000593831:Atxn7 protein, mouse; D002843:Chromatin; D006657:Histones; D009419:Nerve Tissue Proteins