The linker histone H1c contributes to the SCA7 nuclear phenotype

作者：Kizilyaprak Caroline; Spehner Daniele; Devys Didier; Schultz Patrick^*

来源：Nucleus-Austin, 2011, 2(5): 444-454.

DOI：10.4161/nucl.2.5.17843

• SCA7
• histone H1
• photoreceptors
• chromatin structure
• histone modifications
• polyglutamine

Spinocerebellar ataxia type 7 (SCA 7) 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 SCA 7 mouse model expressing mutant ataxin-7 in rod photoreceptors. We analyzed the SCA 7-induced chromatin reorganization by immunogold labeling, stereology, electron tomography and showed that in SCA 7 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 SCA 7 retinas and their cellular distribution appeared similar in wild-type and SCA 7 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 SCA 7 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 SCA 7 rod photoreceptor nuclei.

• 出版日期2011-10