Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation （XLMR） and cleft lip/cleft palate. However, the underl...Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation （XLMR） and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor （RAR）. Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, reeombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 （phenylalanine at position 279 to serine） identified in the XLMR patients is defective in enzymatie activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives PI9 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RAR~ and functions as a coactivator for RARa. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.展开更多
The surface conductivity of poly [ 2-methoxy-5-（3＇-methyl） butoxy]-p-phenylene vinylene （PMOMBOPV） films doped with FeCl3 and H2SO4 by chemical method and implanted by N^＋ ions was studied and the comparison of ...The surface conductivity of poly [ 2-methoxy-5-（3＇-methyl） butoxy]-p-phenylene vinylene （PMOMBOPV） films doped with FeCl3 and H2SO4 by chemical method and implanted by N^＋ ions was studied and the comparison of environmental stability of conductive behavior was also investigated. The energy and dose of N^＋ ions were in the rang 15～35 keV and 3. 8×10^15～9. 6×10^16 ions/cm^2, respectively. The conductivity of PMOMBOPV film was enhanced remarkably with the increases of the energy and dose of N^＋ ions. For example, the conductivity of PMOMBOPV film was 3. 2×10^-2S/cm when ion implantation was performed with an energy of 35 keV at a dose of 9. 6 × 10^14 ions/cm^2 , which was almost seven orders of magnitude higher than that of film unimplanted. The environmental stability of conductive behavior for ionimplanted film was much better than that of chemical doped films. Moreover, the conductive activation energy of ion-implanted films was measured to be about 0.17 eV.展开更多
文摘Recent studies have identified mutations in PHF8, an X-linked gene encoding a JmjC domain-containing protein, as a causal factor for X-linked mental retardation （XLMR） and cleft lip/cleft palate. However, the underlying mechanism is unknown. Here we show that PHF8 is a histone demethylase and coactivator for retinoic acid receptor （RAR）. Although activities for both H3K4me3/2/1 and H3K9me2/1 demethylation were detected in cellularbased assays, reeombinant PHF8 exhibited only H3K9me2/1 demethylase activity in vitro, suggesting that PHF8 is an H3K9me2/1 demethylase whose specificity may be modulated in vivo. Importantly, a mutant PHF8 （phenylalanine at position 279 to serine） identified in the XLMR patients is defective in enzymatie activity, indicating that the loss of histone demethylase activity is causally linked with the onset of disease. In addition, we show that PHF8 binds specifically to H3K4me3/2 peptides via an N-terminal PHD finger domain. Consistent with a role for PHF8 in neuronal differentiation, knockdown of PHF8 in mouse embryonic carcinoma P19 cells impairs RA-induced neuronal differentiation, whereas overexpression of the wild-type but not the F279S mutant PHF8 drives PI9 cells toward neuronal differentiation. Furthermore, we show that PHF8 interacts with RAR~ and functions as a coactivator for RARa. Taken together, our results suggest that histone methylation modulated by PHF8 plays a critical role in neuronal differentiation.
基金National Natural Science Foundation of China (60277002) Scientific Research Foundation of Xi’an JiaotongUniversity
文摘The surface conductivity of poly [ 2-methoxy-5-（3＇-methyl） butoxy]-p-phenylene vinylene （PMOMBOPV） films doped with FeCl3 and H2SO4 by chemical method and implanted by N^＋ ions was studied and the comparison of environmental stability of conductive behavior was also investigated. The energy and dose of N^＋ ions were in the rang 15～35 keV and 3. 8×10^15～9. 6×10^16 ions/cm^2, respectively. The conductivity of PMOMBOPV film was enhanced remarkably with the increases of the energy and dose of N^＋ ions. For example, the conductivity of PMOMBOPV film was 3. 2×10^-2S/cm when ion implantation was performed with an energy of 35 keV at a dose of 9. 6 × 10^14 ions/cm^2 , which was almost seven orders of magnitude higher than that of film unimplanted. The environmental stability of conductive behavior for ionimplanted film was much better than that of chemical doped films. Moreover, the conductive activation energy of ion-implanted films was measured to be about 0.17 eV.
