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Poleshko A , Kossenkov AV , Shalginskikh N , Pecherskaya A , Einarson MB , Marie Skalka A , Katz RA
Human factors and pathways essential for mediating epigenetic gene silencing
Epigenetics. 2014 Sep;9(9) :1280-9
PMID: 25147916   
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Abstract
Cellular identity in both normal and disease processes is determined by programmed epigenetic activation or silencing of specific gene subsets. Here, we have used human cells harboring epigenetically silent GFP-reporter genes to perform a genome-wide siRNA knockdown screen for the identification of cellular factors that are required to maintain epigenetic gene silencing. This unbiased screen interrogated 21,121 genes, and we identified and validated a set of 128 protein factors. This set showed enrichment for functional categories, and protein-protein interactions. Among this set were known epigenetic silencing factors, factors with no previously identified role in epigenetic gene silencing, as well as unstudied factors. The set included non-nuclear factors, for example, components of the integrin-adhesome. A key finding was that the E1 and E2 enzymes of the small ubiquitin-like modifier (SUMO) pathway (SAE1, SAE2/UBA2, UBC9/UBE2I) are essential for maintenance of epigenetic silencing. This work provides the first genome-wide functional view of human factors that mediate epigenetic gene silencing. The screen output identifies novel epigenetic factors, networks, and mechanisms, and provides a set of candidate targets for epigenetic therapy and cellular reprogramming.
Notes
1559-2308 Poleshko, Andrey Kossenkov, Andrew V Shalginskikh, Natalia Pecherskaya, Anna Einarson, Margret B Marie Skalka, Anna Katz, Richard A CA006927/CA/NCI NIH HHS/United States CA071515/CA/NCI NIH HHS/United States DK082498/DK/NIDDK NIH HHS/United States R01 CA071515/CA/NCI NIH HHS/United States Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't United States Epigenetics. 2014 Sep;9(9):1280-9. doi: 10.4161/epi.32088. Epub 2014 Aug 4.