Abstract
The incorporation of histone variants into chromatin plays an important role for the establishment of particular chromatin states. Six human histone H3 variants are known to date, not counting CenH3 variants: H3.1, H3.2, H3.3 and the testis-specific H3.1t as well as the recently described variants H3.X and H3.Y. We report the discovery of H3.5, a novel non-CenH3 histone H3 variant. H3.5 is encoded on human chromosome 12p11.21 and probably evolved in a common ancestor of all recent great apes (Hominidae) as a consequence of H3F3B gene duplication by retrotransposition. H3.5 mRNA is specifically expressed in seminiferous tubules of human testis. Interestingly, H3.5 has two exact copies of ARKST motifs adjacent to lysine-9 or lysine-27, and lysine-79 is replaced by asparagine. In the Hek293 cell line, ectopically expressed H3.5 is assembled into chromatin and targeted by PTM. H3.5 preferentially colocalizes with euchromatin, and it is associated with actively transcribed genes and can replace an essential function of RNAi-depleted H3.3 in cell growth.
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Acknowledgements
Whole chromosome #12 paint was kindly donated by Dr. Marion Cremer, LMU Munich. Bonobo sperm as well as gorilla saliva samples were kindly provided by Dr. Arne Lawrenz, Wuppertal Zoo. Testicular tissue was sampled and kindly provided by Ulrich Gertenbach and Stephan Roth, HELIOS Klinikum Wuppertal, Urology. This work was supported by the HELIOS Research Center.
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Supporting Data 1
Alignment of the protein coding sequences of H3 variant genes used in this study. (JPEG 16451 kb)
Supporting Data 2
Alignment of the H3F3C gene with the mRNA sequences of H3.5 as well as H3.3/H3F3B. (JPEG 2514 kb)
Supporting Data 3
Ectopically expressed H3.5 can replace H3.3 to some extent. a Comparison of doubling times in cells co-transfected with H3F3A/H3F3B siRNAs and the GST-H3.5 expression vector and cells transfected with H3F3A/H3F3B siRNAs only at four successive days. b Nascent BrdU-labelled DNA (green) in cells transfected with H3F3A/H3F3B siRNAs. DAPI (blue) was used for DNA counterstaining. c. Nascent DNA (green) in cells co-transfected with H3F3A/H3F3B siRNAs and the GST-H3.5 expression vector. DAPI (blue) was used for DNA counterstaining. (JPEG 476 kb)
Supporting Data 4
Structural simulation of H3.5 within the nucleosome with emphasis on the chaperone recognition domain. Selected residues are labelled and colour-shaded. (JPEG 809 kb)
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Schenk, R., Jenke, A., Zilbauer, M. et al. H3.5 is a novel hominid-specific histone H3 variant that is specifically expressed in the seminiferous tubules of human testes. Chromosoma 120, 275–285 (2011). https://doi.org/10.1007/s00412-011-0310-4
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DOI: https://doi.org/10.1007/s00412-011-0310-4