Genomic imprinting is an allele-specific gene expression system important for mammalian development and function 1. The molecular basis of genomic imprinting is allele-specific DNA methylation 1,2. While it is well known that the de novo DNA methyltransferases Dnmt3a/b are responsible for the establishment of genomic imprinting 3, how the methylation mark is erased during primordial germ cell (PGC) reprogramming remains a mystery. Tet1 is one of the ten-eleven translocation family proteins, which have the capacity to oxidize 5-methylcytosine (5mC) 4-6, specifically expressed in reprogramming PGCs 7. Here we report that Tet1 plays a critical role in the erasure of genomic imprinting. We show that despite their identical genotype, progenies derived from mating between Tet1-KO males and wild-type females exhibit a number of variable phenotypes including placental, fetal and postnatal growth defects, and early embryonic lethality. These defects are, at least in part, caused by the dysregulation of imprinted genes, such as Peg10 and Peg3, which exhibit aberrant hypermethylation in the paternal allele of differential methylated regions (DMRs). RNA-seq reveals extensive dysregulation of imprinted genes in the next generation due to paternal loss function of Tet1. Genome-wide DNA methylation analysis of E13.5 PGCs and sperms of Tet1-KO mice revealed hypermethylation of DMRs of imprinted genes in sperm, which can be traced back to PGCs. Analysis of the DNA methylation dynamics in reprogramming PGCs suggests that Tet1 functions to wipe out remaining methylation, including imprinted genes, at the late reprogramming stage. We further provide evidence supporting Tet1's role in the erasure of paternal imprints in female germline. Thus, our study establishes a critical function of Tet1 in genomic imprinting erasure.
Commentary on: Shapiro S, Rotter M. Graphic depictions: portrayals of mental illness in video games. J Forensic Sci 2016;61 (6):1592-5.
Sir,This commentary is in response to the study of Shapiro and Rotter (2016): "Graphic Depictions: Portrayals of Mental Illness in Video Games." (1) The article elicits a particularly painful reminder about the misrepresentation of mental illness in various sociocultural establishments, such as writings, popular media, and tools of entertainment such as video games. My group's research is closely related to the context of the authors' analysis of the portrayal of mental illness in the age of technology.Recently, we conducted a study of the people who video-blogged about experiencing suicidal ideations. The goal was to understand how these individuals represent their mental illness, and how the audience responds to this imagery. Similar to methods described in the article of Shapiro and Rotter, a student of mine and I selectively searched the Web, identifying over 100 video blogs featuring suicidal struggle. All bloggers (n = 103) were invited to participate in the study. Of those, 24 individuals agreed to take part in semistructured interviews, conducted in English through a secure video chat.After transcribing verbatim all interviews, we conducted a qualitative content analysis of each blog profile, noting trends of perceiving psychiatric struggle on the Internet. We made a few general observations. First, people with suicidal thoughts post online about their mental illness to attract attention and receive spiritual support. Second, over 72% of audience comments of each blog post encouraged act of suicide. Third, about 21% showed some remorse through their comments-mixed neutral and positive responses. Fourth, only 6% of comments were supportive and clearly discouraged suicide.In the text analysis of the history of site activity, not a single person triggered an emergency note to police to alarm about events of suicidal plans occurring online. In fact, more than two-thirds of the commenters RSVP'd to watch live-streamed suicidal attempt of each of our participants. These data paint a disturbing picture of callous Internet users who follow suicidal bloggers for entertainment. These observations show disregard for mental illness in online space and that people who search for support online are more likely to be encouraged into self-destructive behaviors.
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