Successful Transmission and Transcriptional Deployment of A
RESEARCH ARTICLE Successful transmission and transcriptional deployment of a human chromosome via mouse male meiosis Christina Ernst1, Jeremy Pike1, Sarah J Aitken1,2, Hannah K Long3,4,5, Nils Eling1, Lovorka Stojic1, Michelle C Ward1, Frances Connor1, Timothy F Rayner1, Margus Lukk1, Robert J Klose3, Claudia Kutter6, Duncan T Odom1* 1Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom; 2Department of Histopathology, Addenbrooke’s Hospital, Cambridge, United Kingdom; 3Department of Biochemistry, University of Oxford, Oxford, United Kingdom; 4Institute of Stem Cell Biology and Regenerative Medicine, Stanford University School of Medicine, Stanford, United states; 5Department of Chemical and Systems Biology, Stanford University School of Medicine, Stanford, United States; 6Department of Microbiology, Tumor and Cell Biology, Science for Life Laboratory, Karolinska Institute, Stockholm, Sweden Abstract Most human aneuploidies originate maternally, due in part to the presence of highly stringent checkpoints during male meiosis. Indeed, male sterility is common among aneuploid mice used to study chromosomal abnormalities, and male germline transmission of exogenous DNA has been rarely reported. Here we show that, despite aberrant testis architecture, males of the aneuploid Tc1 mouse strain produce viable sperm and transmit human chromosome 21 to create aneuploid offspring. In these offspring, we mapped transcription, transcriptional initiation, enhancer activity, non-methylated DNA, and transcription factor
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