We aim to understand the molecular mechanisms behind epigenetic silencing. We use several model systems to study the interaction between known and novel epigenetic modifiers: X inactivation, genomic imprinting, and embryonic development.

In each case, we seek to understand how epigenetic modifiers elicit transcriptional silencing, and how this relates to functional outcomes for the cell. We use a combination of genetic, genomic and advanced imaging techniques to address these questions.

By studying the molecular mechanisms governing epigenetic control in normal development, we hope to understand how it goes awry in disease. This may reveal how we can manipulate epigenetic state for therapeutic gain.

Our current focus is the epigenetic regulator SMCHD1. We are screening for small molecule activators and inhibitors of SMCHD1: the former as potential treatments for facioscapulohumeral muscular dystrophy, the latter for Prader Willi and Schaaf-Yang syndromes. These diseases have no current targeted treatments and remain incurable.


Selected publications from Prof Marnie Blewitt

N Benetti, Q Gouil, A Tapia Del Fierro, T Beck, K Breslin, A Keniry, E McGlinn*, ME BLEWITT*. Maternal SMCHD1 regulates Hox gene expression and patterning in the mouse embryo. NATURE COMMUNICATIONS. 2022 Jul 25;13(1):4295.

A Keniry*, N Jansz, PF Hickey, K Breslin, M Iminitoff, T Beck, QA Gouil, ME Ritchie, ME BLEWITT*. A method for stabilising the XX karyotype in female mESC cultures. DEVELOPMENT 2022 Nov 15;149(22)

A Keniry*, N Jansz, LJ Gearing, I Wanigasuriya, J Chen, CM Nefzger, PF Hickey, Q Gouil, J Liu, KA Breslin, M Iminitoff, T Beck, A Tapia del Fierro, L Whitehead, A Jarratt, SA Kinkel, PC Taberlay, T Willson, M Pakusch, ME Ritchie, DJ Hilton, JM Polo, ME BLEWITT* Xmas mESC: A female embryonic stem cell system that reveals the BAF complex as a key regulator of establishment of X chromosome inactivation. NATURE COMMUNICATIONS 2022 Mar 29;13(1):1658

I Wanigasuriya*, QA Gouil*, SA Kinkel, A Tapia Del Fierro, T Beck, EA Roper, K Breslin, J Stringer, K Hutt, HJ Lee, A Keniry, ME Ritchie, ME BLEWITT. Smchd1 is a maternal effect gene required for genomic imprinting. eLIFE 2020 Nov 13;9:e55529

N Jansz, T Nesterova, A Keniry, M Iminitoff, PF Hickey, G Pintacuda, O Masui, S Kolbeke, N Geoghegan, KA Breslin, TA Willson, K Rogers, GF Kay, AH Fox, H Koseki, N Brockdorff, JM Murphy, ME BLEWITT. Smchd1 targeting to the inactive X is dependent on the Xist-HnrnpK-PRC1 pathway. CELL REPORTS 2018 Nov 1;25(7):1912-192

N Jansz, A Keniry, M Trussart, H. Bildsoe, T. Beck, ID Tonks, AW Mould, P Hickey, K Breslin, M Iminitoff, ME Ritchie, E McGlinn, GF Kay, JM Murphy and ME Blewitt Smchd1 regulates long-range chromatin interactions on the inactive X chromosome and at Hox clusters. NAT STRUCT MOL BIOL 2018 25, 766-777

CT Gordon^, S Xue^, G Yigit^, H Filali^, K Chen^, N Rosin, KI Yoshiura, M Oufadem, TJ Beck, R McGowan, AC Magee, J Altmüller, C Dion, H Thiele, AD Gurzau, … JM Murphy, C Chatdokmaiprai, AM Hillmer, D Wattanasirichaigoon, S Lyonnet, F Magdinier, A Javed*, ME BLEWITT*, J Amiel*, B Wollnik*, B Reversade* De novo mutations in SMCHD1 cause Bosma arhinia microphthalmia syndrome and abrogate nasal development. NATURE GENETICS 2017 Feb;49(2):249-255

K Chen, J Hu, DL Moore, R Liu, SA Kessans, K Breslin, IS Lucet, A Keniry, HS Leong, CL Parish, DJ Hilton, RJ Lemmers, SM van der Maarel, PE Czabotar, RC Dobson, ME Ritchie, GF Kay*, JM Murphy*, ME BLEWITT* Genome-wide binding and mechanistic analyses of Smchd1-mediated epigenetic regulation. PROC NATL ACAD SCI USA 2015 Jul 7;112(27):55-44

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