Life Sciences Research for Lifelong Health

Patrick Varga-Weisz

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.

HeterochromatinKey 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 Publication:
ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior
Nature Medicine Advance Online Publication 21 Sep 2015
http://dx.doi.org/10.1038/nm.3939

Latest Publications

ACF chromatin-remodeling complex mediates stress-induced depressive-like behavior.
Sun H, Damez-Werno DM, Scobie KN, Shao NY, Dias C, Rabkin J, Koo JW, Korb E, Bagot RC, Ahn FH, Cahill ME, Labonté B, Mouzon E, Heller EA, Cates H, Golden SA, Gleason K, Russo SJ, Andrews S, Neve R, Kennedy PJ, Maze I, Dietz DM, Allis CD, Turecki G, Varga-Weisz P, Tamminga C, Shen L, Nestler EJ

Improved treatment for major depressive disorder (MDD) remains elusive because of the limited understanding of its underlying biological mechanisms. It is likely that stress-induced maladaptive transcriptional regulation in limbic neural circuits contributes to the development of MDD, possibly through epigenetic factors that regulate chromatin structure. We establish that persistent upregulation of the ACF (ATP-utilizing chromatin assembly and remodeling factor) ATP-dependent chromatin-remodeling complex, occurring in the nucleus accumbens of stress-susceptible mice and depressed humans, is necessary for stress-induced depressive-like behaviors. We found that altered ACF binding after chronic stress was correlated with altered nucleosome positioning, particularly around the transcription start sites of affected genes. These alterations in ACF binding and nucleosome positioning were associated with repressed expression of genes implicated in susceptibility to stress. Together, our findings identify the ACF chromatin-remodeling complex as a critical component in the development of susceptibility to depression and in regulating stress-related behaviors.

+ View Abstract

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, Hogan CJ, Guillaume C, Ke H, Brandetti E, Walker S, Koohy H, Spivakov M, Varga-Weisz P

Endocytosis is essential for uptake of many substances into the cell, but how it links to nutritional signalling is poorly understood. Here we show a novel role for endocytosis in regulating the response to low phosphate in Schizosaccharomyces pombe. Loss of function of Myo1, Sla2/End4 or Arp2, proteins involved in the early steps of endocytosis, led to increased proliferation in low phosphate media compared to controls. We show that once cells are deprived of phosphate they undergo a quiescence response that is dependent on the endocytic function of Myo1. Transcriptomic analysis revealed a wide perturbation of gene expression with induction of stress-regulated genes upon phosphate starvation in wildtype but not Δmyo1 cells. Thus, endocytosis plays a pivotal role in mediating the cellular response to nutrients, bridging the external environment and internal molecular functions of the cell.

+ View Abstract

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

 

Group Members

Latest Publications

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

Fission yeast Iec1-ino80-mediated nucleosome eviction regulates nucleotide and phosphate metabolism.

CJ Hogan, S Aligianni, M Durand-Dubief

Molecular and cellular biology
30 3:657-74 (2010)

DOI: 10.1128/MCB.01117-09

PMID: 19933844

The regulation of ATP-dependent nucleosome remodelling factors.

C Hogan, P Varga-Weisz

Mutation research
618 1-2:41-51 (2007)

DOI: 10.1016/j.mrfmmm.2006.07.010

PMID: 17306842

Regulation of higher-order chromatin structures by nucleosome-remodelling factors.

PD Varga-Weisz, PB Becker

Current opinion in genetics & development
16 2:151-6 (2006)

DOI: 10.1016/j.gde.2006.02.006

PMID: 16503135