分类： 生物学 >> 生物物理学 提交时间： 2016-05-11
Guo, Xue
Wang, Ling
Li, Jie
Xiao, Jianxiong
Yin, Xiaotong
He, Shuang
Xu, Yanhui
Guo, Xue
Wang, Ling
Xu, Yanhui
Ding, Zhanyu
Cong, Yao
Shi, Pan
Tian, Changlin
Shi, Pan
Tian, Changlin
Shi, Pan
Tian, Changlin
Dong, Liping
Li, Guohong
摘要： DNA methylation is an important epigenetic modification that is essential for various developmental processes through regulating gene expression, genomic imprinting, and epigenetic inheritance(1-5). Mammalian genomic DNA methylation is established during embryogenesis by de novo DNA methyltransferases, DNMT3A and DNMT3B(6-8), and the methylation patterns vary with developmental stages and cell types(9-12). DNAmethyltransferase 3-like protein (DNMT3L) is a catalytically inactive paralogue of DNMT3 enzymes, which stimulates the enzymatic activity of Dnmt3a(13). Recent studies have established a connection between DNA methylation and histone modifications, and revealed a histone-guided mechanism for the establishment of DNA methylation(14). The ATRX-DNMT3-DNMT3L (ADD) domain of Dnmt3a recognizes unmethylated histone H3 (H3K4me0)(15-17). The histone H3 tail stimulates the enzymatic activity of Dnmt3a in vitro(17,18), whereas the molecular mechanism remains elusive. Here we show that DNMT3A exists in an autoinhibitory form and that the histone H3 tail stimulates its activity in a DNMT3L-independent manner. We determine the crystal structures of DNMT3A-DNMT3L (autoinhibitory form) and DNMT3A-DNMT3L-H3 (active form) complexes at 3.82 and 2.90 angstrom resolution, respectively. Structural and biochemical analyses indicate that the ADD domain of DNMT3A interacts with and inhibits enzymatic activity of the catalyticdomain (CD) through blocking its DNA-binding affinity. HistoneH3(but not H3K4me3) disrupts ADD-CD interaction, induces a large movement of the ADD domain, and thus releases the autoinhibition of DNMT3A. The finding adds another layer of regulation of DNA methylation to ensure that the enzyme is mainly activated at proper targeting loci when unmethylated H3K4 is present, and strongly supports a negative correlation between H3K4me3 and DNA methylation across the mammalian genome(9,10,19,20). Our study provides a new insight into an unexpected autoinhibition and histone H3-induced activation of the de novo DNA methyltransferase after its initial genomic positioning.
分类： 地球科学 >> 空间物理学 提交时间： 2016-05-13
摘要： Superhalo electrons appear to be continuously present in the interplanetary medium, even during very quiet times, with a power-law spectrum at energies above similar to 2 keV. Here we numerically investigate the generation of superhalo electrons by magnetic reconnection in the solar wind source region, using magnetohydrodynamics and test particle simulations for both single X-line reconnection and multiple X-line reconnection. We find that the direct current electric field, produced in the magnetic reconnection region, can accelerate electrons from an initial thermal energy of T similar to 10(5) K up to hundreds of keV. After acceleration, some of the accelerated electrons, together with the nascent solar wind flow driven by the reconnection, propagate upwards along the newly-opened magnetic field lines into interplanetary space, while the rest move downwards into the lower atmosphere. Similar to the observed superhalo electrons at 1 AU, the flux of upward-traveling accelerated electrons versus energy displays a power-law distribution at similar to 2 - 100 keV, f (E) similar to E-delta, with a delta of similar to 1.5 - 2.4. For single (multiple) X-line reconnection, the spectrum becomes harder (softer) as the anomalous resistivity parameter alpha (uniform resistivity eta) increases. These modeling results suggest that the acceleration in the solar wind source region may contribute to superhalo electrons.
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