Life Sciences Research for Lifelong Health

Patrick Varga-Weisz

As of April 2018, Patrick has taken up a Lectureship in the School of Biological Sciences at the University of Essex. Visit his page there for full details of his current research.

Research Summary

​Chromatin is a highly dynamic structure to accommodate its many tasks in regulating, organizing, safeguarding and packaging the genetic material. We are interested in understanding the mechanisms behind this sophisticated cellular machinery.

Key components that impart this dynamic state are special enzymes, so called chromatin remodelling factors, many of which target the nucleosome, the basic building block of chromatin.

The enzymology of chromatin remodelling is a largely new territory with opportunities for many exciting discoveries. One particular class of chromatin remodelling factors uses the energy gained by ATP hydrolysis to remodel nucleosomes: The nucleosome may be shifted, altered or blasted away, but some of these factors, such as Imitation Switch (ISWI), are also involved in nucleosome assembly.

The Varga-Weisz laboratory studies such ATP-dependent nucleosome remodelling factors, their role in the cell (in chromatin replication) and their mechanisms of action.

Latest Publications

A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.
Rodrigues C, Pattabiraman C, Vijaykumar A, Arora R, Narayana SM, Kumar RV, Notani D, Varga-Weisz P, Krishna S

Metastatic progression is a major cause of mortality in cervical cancers, but factors regulating migratory and pre-metastatic cell populations remain poorly understood. Here, we sought to assess whether a SUV39H1-low chromatin state promotes migratory cell populations in cervical cancers, using meta-analysis of data from The Cancer Genome Atlas (TCGA), immunohistochemistry, genomics and functional assays. Cervical cancer cells sorted based on migratory ability in vitro have low levels of SUV39H1 protein, and SUV39H1 knockdown in vitro enhanced cervical cancer cell migration. Further, TCGA SUV39H1-low tumours correlated with poor clinical outcomes and showed gene expression signatures of cell migration. SUV39H1 expression was examined within biopsies, and SUV39H1 cells within tumours also demonstrated migratory features. Next, to understand genome scale transcriptional and chromatin changes in migratory populations, cell populations sorted based on migration in vitro were examined using RNA-Seq, along with ChIP-Seq for H3K9me3, the histone mark associated with SUV39H1. Migrated populations showed SUV39H1-linked migratory gene expression signatures, along with broad depletion of H3K9me3 across gene promoters. We show for the first time that a SUV39H1-low chromatin state associates with, and promotes, migratory populations in cervical cancers. Our results posit SUV39H1-low cells as key populations for prognosis estimation and as targets for novel therapies.

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Experimental cell research, , 1090-2422, , 2019

PMID: 30772380

Enzymatic Assays of Histone Decrotonylation on Recombinant Histones.
Fellows R, Varga-Weisz P

Class I histone deacetylases (HDACs) are efficient histone decrotonylases, broadening the enzymatic spectrum of these important (epi-)genome regulators and drug targets. Here, we describe an approach to assaying class I HDACs with different acyl-histone substrates, including crotonylated histones and expand this to examine the effect of inhibitors and estimate kinetic constants.

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Bio-protocol, 8, 2331-8325, , 2018

PMID: 30283810

Genome organization and chromatin analysis identify transcriptional downregulation of insulin-like growth factor signaling as a hallmark of aging in developing B cells.
Koohy H, Bolland DJ, Matheson LS, Schoenfelder S, Stellato C, Dimond A, Várnai C, Chovanec P, Chessa T, Denizot J, Manzano Garcia R, Wingett SW, Freire-Pritchett P, Nagano T, Hawkins P, Stephens L, Elderkin S, Spivakov M, Fraser P, Corcoran AE, Varga-Weisz PD

Aging is characterized by loss of function of the adaptive immune system, but the underlying causes are poorly understood. To assess the molecular effects of aging on B cell development, we profiled gene expression and chromatin features genome-wide, including histone modifications and chromosome conformation, in bone marrow pro-B and pre-B cells from young and aged mice.

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Genome biology, 19, 1474-760X, 126, 2018

PMID: 30180872

 

Group Members

Latest Publications

A SUV39H1-low chromatin state characterises and promotes migratory properties of cervical cancer cells.

Rodrigues C, Pattabiraman C, Vijaykumar A

Experimental cell research
1090-2422: (2019)

PMID: 30772380

Enzymatic Assays of Histone Decrotonylation on Recombinant Histones.

Fellows R, Varga-Weisz P

Bio-protocol
8 2331-8325: (2018)

PMID: 30283810

Microbiota derived short chain fatty acids promote histone crotonylation in the colon through histone deacetylases.

Fellows R, Denizot J, Stellato C

Nature communications
9 2041-1723:105 (2018)

PMID: 29317660

ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.

Sun H, Damez-Werno DM, Scobie KN

Nature medicine
1546-170X: (2015)

PMID: 26390241

A novel phosphate-starvation response in fission yeast requires the endocytic function of Myosin I.

Petrini E, Baillet V, Cridge J

Journal of cell science
1477-9137: (2015)

PMID: 26345368

Chromatin remodeling: a collaborative effort.

Varga-Weisz PD

Nature structural & molecular biology
21 1545-9985:14-6 (2014)

PMID: 24389547

Keeping chromatin quiet: how nucleosome remodeling restores heterochromatin after replication.

JE Mermoud, SP Rowbotham, PD Varga-Weisz

Cell cycle (Georgetown, Tex.)
10 23:4017-25 (2011)

DOI: 10.4161/cc.10.23.18558

PMID: 22101266

Insights into how chromatin remodeling factors find their target in the nucleus.

PD Varga-Weisz

Proceedings of the National Academy of Sciences of the United States of America
107 46:19611-2 (2010)

DOI: 10.1073/pnas.1014956107

PMID: 21059914

The SNF2-family member Fun30 promotes gene silencing in heterochromatic loci.

A Neves-Costa, WR Will, AT Vetter

PloS one
4 12:e8111 (2009)

DOI: 10.1371/journal.pone.0008111

PMID: 19956593