Enhancers are essential gene regulatory elements whose alteration can lead to morphological differences between species, developmental abnormalities, and human disease. Current strategies to identify enhancers focus primarily on noncoding sequences and tend to exclude protein coding sequences. Here, we analyzed 25 available ChIP-seq data sets that identify enhancers in an unbiased manner (H3K4me1, H3K27ac, and EP300) for peaks that overlap exons. We find that, on average, 7% of all ChIPseq peaks overlap coding exons (after excluding for peaks that overlap with first exons). By using mouse and zebrafish enhancer assays, we demonstrate that several of these exonic enhancer (eExons) candidates can function as enhancers of their neighboring genes and that the exonic sequence is necessary for enhancer activity. Using ChIP, 3C, and DNA FISH, we further show that one of these exonic limb enhancers, Dync1i1 exon 15, has active enhancer marks and physically interacts with Dlx5/6 promoter regions 900 kb away. In addition, its removal by chromosomal abnormalities in humans could cause split hand and foot malformation 1 (SHFM1), a disorder associated with DLX5/6. These results demonstrate that DNA sequences can have a dual function, operating as coding exons in one tissue and enhancers of nearby gene(s) in another tissue, suggesting that phenotypes resulting from coding mutations could be caused not only by protein alteration but also by disrupting the regulation of another gene.
The lifetime of the emission of a single electron stored in a nanocrystalline Si ͑nc-Si͒ dot has been studied in order to understand the physical processes for memory applications. A small active area field effect transistor channel ͑50ϫ25 nm͒ is defined by electron-beam lithography on a thin ͑20 nm͒ silicon-on-insulator channel and allows for the electrical isolation of a single nc-Si dot. Remote plasma enhanced chemical vapor deposition is used to form 8Ϯ1 nm diameter nc-Si dots in the gas phase from a pulsed SiH 4 source. Electrons stored in a dot results in an observed discrete threshold shift of 90 mV. Analysis of lifetime as a function of applied potential and temperature show the dot to be an acceptor site with nearly Poisson time distributions. An observed 1/T 2 dependence of lifetime is consistent with a direct tunneling process, and interface states are not the dominant mechanism for electron storage in this device structure. Median emission lifetimes as a function of applied gate bias are readily modeled by the polarizability of an electron in a delocalized bound state over the entire semiconducting dot.
We demonstrate 50-Gb/s direct modulation by using 1.3-μm distributed-feedback lasers with a ridge waveguide structure. We employed InGaAlAs material for a multiple-quantum well to obtain a low damping factor K, and fabricated a ridge waveguide structure buried in benzocyclobutene to realize a structure with a low parasitic capacitance. In addition, to obtain high maximum frequency relaxation oscillations fr, we designed the cavity length L), and achieved a 3-dB-down frequency bandwidth of 34 GHz. We realized 50-Gb/s clear eye openings with a back-toback configuration, and achieved a mean output power of over 5.0 dBm, and a dynamic extinction ratio of 4.5 dB. We measured the 50-Gb/s transmission characteristics, and obtained clear eye openings for transmissions over 20-, 40-, and 60-km single-mode fibers (SMF). We also measured the bit-error-rate performance, and obtained an error-free operation and a power penalty of less than 0.5 dB after a 10-km SMF transmission.
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