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. 2017 Dec 21;27(4):649–666. doi: 10.1093/hmg/ddx432

Figure 6.

Figure 6.

Direct manipulation of the H3K27 residue by PTM mimetic exert minor influence on HD pathology. The effects of H3K27 modifications on mutant Htt-induced reduced longevity and impaired motor activity were investigated in flies co-expressing UAS-Httex1p-Q93 and wild-type or point mutant UAS-His3.3A (wtHis3.3A, His3.3A-K27R or His3.3A-K27M) in the nervous system in a hetero- or homozygous His3.3AKO background. (A) Survival plot shows percent survival of Httex1p-Q93 expressing males heterozygous for His3.3AKO and co-expressing wtH3.3A (n = 185), H3.3A-K27R (n = 225) or H3.3A-K27M (n = 255) as a function of time. (B) In heterozygous His3.3AKO background expression of His3.3A-K27R slightly but significantly increases longevity (P = 0.0426, log-rank test) of HD flies. Bars show restricted mean lifespan. Error bars represent SEM. (C) Percent survival of Httex1p-Q93 expressing males homozygous for His3.3AKO and co-expressing wtH3.3A (n = 201), H3.3A-K27R (n = 234) or H3.3A-K27M (n = 216) as a function of time. (D) In homozygous His3.3AKO background expression of His3.3A-K27M significantly decreases longevity (P = 0.0009, log-rank test) of HD flies. Restricted mean lifespan is shown. Error bars represent standard error of mean. (E) Motor activity of flies co-expressing UAS-Httex1p and wild-type or point mutant UAS-His3.3A were analyzed by the climbing assay. No significant difference between HD flies expressing wtH3.3A, H3.3A-K27R or H3.3A-K27M was found for the capability to climb at least 2.5, 5 or 7.5 cm vertically in 10 s.