Developmentally Regulated Linker Histone H1c Promotes Heterochromatin Condensation and Mediates Structural Integrity of Rod Photoreceptors in Mouse Retina

Mature rod photoreceptor cells contain very small nuclei with tightly condensed heterochromatin. We observed that during mouse rod maturation, the nucleosomal repeat length increases from 190 bp at postnatal day 1 to 206 bp in the adult retina. At the same time, the total level of linker histone H1...

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Bibliographic Details
Published in:The Journal of biological chemistry 2013-06, Vol.288 (24), p.17895-17907
Main Authors: Popova, Evgenya Y., Grigoryev, Sergei A., Fan, Yuhong, Skoultchi, Arthur I., Zhang, Samuel S., Barnstable, Colin J.
Format: Article
Language:English
Subjects:
Animals
Cell Nucleus - metabolism
Chromatin Assembly and Disassembly
Development
Developmental Biology
Epigenesis, Genetic
Female
Gene Expression Regulation, Developmental
Gene Knockout Techniques
Heterochromatin
Heterochromatin - metabolism
Histone H1c
Histones
Histones - genetics
Histones - metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Nucleosomes - metabolism
Photoreceptors
Repetitive Sequences, Nucleic Acid - genetics
Retina
Retina - cytology
Retina - growth & development
Retina Development
Retinal Rod Photoreceptor Cells - metabolism
Rod Photoreceptor
Transcription, Genetic
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Summary:Mature rod photoreceptor cells contain very small nuclei with tightly condensed heterochromatin. We observed that during mouse rod maturation, the nucleosomal repeat length increases from 190 bp at postnatal day 1 to 206 bp in the adult retina. At the same time, the total level of linker histone H1 increased reaching the ratio of 1.3 molecules of total H1 per nucleosome, mostly via a dramatic increase in H1c. Genetic elimination of the histone H1c gene is functionally compensated by other histone variants. However, retinas in H1c/H1e/H10 triple knock-outs have photoreceptors with bigger nuclei, decreased heterochromatin area, and notable morphological changes suggesting that the process of chromatin condensation and rod cell structural integrity are partly impaired. In triple knock-outs, nuclear chromatin exposed several epigenetic histone modification marks masked in the wild type chromatin. Dramatic changes in exposure of a repressive chromatin mark, H3K9me2, indicate that during development linker histone plays a role in establishing the facultative heterochromatin territory and architecture in the nucleus. During retina development, the H1c gene and its promoter acquired epigenetic patterns typical of rod-specific genes. Our data suggest that histone H1c gene expression is developmentally up-regulated to promote facultative heterochromatin in mature rod photoreceptors. Background: Heterochromatin condenses in the middle of rod cell nuclei during retina maturation. Results: The level of linker histone H1c increases during retina maturation. Rod photoreceptors in triple H1 knock-out mice have less compact chromatin. Conclusion: H1c is a key architectural factor for chromatin condensation in the rod photoreceptor. Significance: Histone H1c expression may be genetically modified to promote rod photoreceptor maturation and retina integrity.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M113.452144