Every gene in (almost) every cell of the body is present in two variants – so called alleles: one is deriving from the mother, the other one from the father. In most cases both alleles are active and transcribed by the cells into an RNA message. However, for a few genes, only one allele is expressed, while the other one is silenced. For long it was thought that the pattern of active alleles is nearly homogeneous in the various tissues of the organism.
The new study (DOI:10.7554/eLife.25125), where CeMM PhD Student Daniel Andergassen is first author (now a PostDoc at Harvard University), uncovers a different picture. By performing the first comprehensive analysis of all active alleles in 23 different tissues and developmental stages of mice, the team of scientists revealed that each tissue showed a specific distribution of active alleles. The scientists were able to catalogue active alleles in a comprehensive set of mouse tissues, or the mouse “Allelome”, and gain an insight into how this differential gene activity is regulated.
The scientists found that both genetic and epigenetic differences between the maternal and paternal allele contributed to the observed tissue-specific activity patterns. This study reveals for the first time a comprehensive picture of all active alleles in different tissues. The results are not only valuable to understand basic biological functions, but will also help investigating diseases that involve defective gene regulators.
Interestingly, this study demonstrated that Igfr2, the first imprinted gene discovered by Denise Barlow in 1991, is surrounding by a large cluster of imprinted genes that extend over 10% of the chromosome, making it the largest co-regulated domain in the genome outside of the X chromosome. Fittingly, after her lab found the first imprinted gene, and discovered the first imprinted non-coding RNA shown to control imprinted silencing, the final work from Denise Barlow’s lab as she went into retirement reveals the full picture of imprinted genes in the mouse.
Daniel Andergassen, Christoph P Dotter, Daniel Wenzel, Verena Sigl, Philipp C Bammer, Markus Muckenhuber, Daniela Mayer, Tomasz M Kulinski, Hans-Christian Theussl, Josef M Penninger, Christoph Bock, Denise P Barlow, Florian M Pauler, Quanah J Hudson. Mapping the mouse Allelome reveals tissue-specific regulation of allelic expression. eLife, August 14, 2017. DOI:10.7554/eLife.25125
This study was supported by the Austrian Science Fund FWF.
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