Browsing by Subject "Terminal Repeat Sequences"

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    Inactivation of the von Hippel-Lindau tumor suppressor leads to selective expression of a human endogenous retrovirus in kidney cancer.
    (Oncogene, 2011-11-24) Cherkasova, E; Malinzak, E; Rao, S; Takahashi, Y; Senchenko, VN; Kudryavtseva, AV; Nickerson, ML; Merino, M; Hong, JA; Schrump, DS; Srinivasan, R; Linehan, WM; Tian, X; Lerman, MI; Childs, RW
    A human endogenous retrovirus type E (HERV-E) was recently found to be selectively expressed in most renal cell carcinomas (RCCs). Importantly, antigens derived from this provirus are immunogenic, stimulating cytotoxic T cells that kill RCC cells in vitro and in vivo. Here, we show HERV-E expression is restricted to the clear cell subtype of RCC (ccRCC) characterized by an inactivation of the von Hippel-Lindau (VHL) tumor-suppressor gene with subsequent stabilization of hypoxia-inducible transcription factors (HIFs)-1α and -2α. HERV-E expression in ccRCC linearly correlated with HIF-2α levels and could be silenced in tumor cells by either transfection of normal VHL or small interfering RNA inhibition of HIF-2α. Using chromatin immunoprecipitation, we demonstrated that HIF-2α can serve as transcriptional factor for HERV-E by binding with HIF response element (HRE) localized in the proviral 5' long terminal repeat (LTR). Remarkably, the LTR was found to be hypomethylated only in HERV-E-expressing ccRCC while other tumors and normal tissues possessed a hypermethylated LTR preventing proviral expression. Taken altogether, these findings provide the first evidence that inactivation of a tumor suppressor gene can result in aberrant proviral expression in a human tumor and give insights needed for translational research aimed at boosting human immunity against antigenic components of this HERV-E.
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    The genome of a songbird.
    (Nature, 2010-04-01) Warren, Wesley C; Clayton, David F; Ellegren, Hans; Arnold, Arthur P; Hillier, Ladeana W; Künstner, Axel; Searle, Steve; White, Simon; Vilella, Albert J; Fairley, Susan; Heger, Andreas; Kong, Lesheng; Ponting, Chris P; Jarvis, Erich D; Mello, Claudio V; Minx, Pat; Lovell, Peter; Velho, Tarciso AF; Ferris, Margaret; Balakrishnan, Christopher N; Sinha, Saurabh; Blatti, Charles; London, Sarah E; Li, Yun; Lin, Ya-Chi; George, Julia; Sweedler, Jonathan; Southey, Bruce; Gunaratne, Preethi; Watson, Michael; Nam, Kiwoong; Backström, Niclas; Smeds, Linnea; Nabholz, Benoit; Itoh, Yuichiro; Whitney, Osceola; Pfenning, Andreas R; Howard, Jason; Völker, Martin; Skinner, Bejamin M; Griffin, Darren K; Ye, Liang; McLaren, William M; Flicek, Paul; Quesada, Victor; Velasco, Gloria; Lopez-Otin, Carlos; Puente, Xose S; Olender, Tsviya; Lancet, Doron; Smit, Arian FA; Hubley, Robert; Konkel, Miriam K; Walker, Jerilyn A; Batzer, Mark A; Gu, Wanjun; Pollock, David D; Chen, Lin; Cheng, Ze; Eichler, Evan E; Stapley, Jessica; Slate, Jon; Ekblom, Robert; Birkhead, Tim; Burke, Terry; Burt, David; Scharff, Constance; Adam, Iris; Richard, Hugues; Sultan, Marc; Soldatov, Alexey; Lehrach, Hans; Edwards, Scott V; Yang, Shiaw-Pyng; Li, Xiaoching; Graves, Tina; Fulton, Lucinda; Nelson, Joanne; Chinwalla, Asif; Hou, Shunfeng; Mardis, Elaine R; Wilson, Richard K
    The zebra finch is an important model organism in several fields with unique relevance to human neuroscience. Like other songbirds, the zebra finch communicates through learned vocalizations, an ability otherwise documented only in humans and a few other animals and lacking in the chicken-the only bird with a sequenced genome until now. Here we present a structural, functional and comparative analysis of the genome sequence of the zebra finch (Taeniopygia guttata), which is a songbird belonging to the large avian order Passeriformes. We find that the overall structures of the genomes are similar in zebra finch and chicken, but they differ in many intrachromosomal rearrangements, lineage-specific gene family expansions, the number of long-terminal-repeat-based retrotransposons, and mechanisms of sex chromosome dosage compensation. We show that song behaviour engages gene regulatory networks in the zebra finch brain, altering the expression of long non-coding RNAs, microRNAs, transcription factors and their targets. We also show evidence for rapid molecular evolution in the songbird lineage of genes that are regulated during song experience. These results indicate an active involvement of the genome in neural processes underlying vocal communication and identify potential genetic substrates for the evolution and regulation of this behaviour.