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Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins

Pradeepa, MM and Grimes, GR and Taylor, GCA and Sutherland, HG and Bickmore, WA (2014) 'Psip1/Ledgf p75 restrains Hox gene expression by recruiting both trithorax and polycomb group proteins.' Nucleic Acids Research, 42 (14). 9021 - 9032. ISSN 0305-1048

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Trithorax and polycomb group proteins are generally thought to antagonize one another. The trithorax familymember MLL (myeloid/lymphoid or mixedlineage leukemia) is presumed to activate Hox expression, counteracting polycomb-mediated repression. PC4 and SF2 interacting protein 1 (PSIP1)/p75, also known as LEDGF, whose PWWP domain binds to H3K36me3, interacts with MLL and tethers MLL fusion proteins toHOXA9 in leukaemias. Here we show, unexpectedly, that Psip1/p75 regulates homeotic genes by recruiting not only MLL complexes, but also the polycomb group protein Bmi1. In Psip1-/- cells binding of Mll1/2, Bmi1 and the co-repressor Ctbp1 at Hox loci are all abrogated and Hoxa and Hoxd mRNA expression increased. Our data not only reveal a potential mechanism of action for Psip1 in the regulation of Hox genes but also suggest an unexpected interplay between proteins usually considered as transcriptional activators and repressors. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Item Type: Article
Subjects: Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science and Health > Biological Sciences, School of
Depositing User: Jim Jamieson
Date Deposited: 23 Nov 2015 10:43
Last Modified: 19 Feb 2019 11:15

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