Skip to main content

Research Repository

Advanced Search

Invadolysin acts genetically via the SAGA complex to modulate chromosome structure

Janiszewski, Michal M.; Heck, Margarete M.S.; Rao, Shubha Gururaja; Janiszewski, Michael M; Duca, Edward; Nelson, Bryce; Abhinav, Kanishk; Panagakou, Ioanna; Vass, Sharron; Heck, Margaret M S


Michal M. Janiszewski

Margarete M.S. Heck

Shubha Gururaja Rao

Michael M Janiszewski

Edward Duca

Bryce Nelson

Kanishk Abhinav

Ioanna Panagakou

Margaret M S Heck


Identification of components essential to chromosome structure and behaviour remains a vibrant area of study. We have previously shown that invadolysin is essential in Drosophila, with roles in cell division and cell migration. Mitotic chromosomes are hypercondensed in length, but display an aberrant fuzzy appearance. We additionally demonstrated that in human cells, invadolysin is localized on the surface of lipid droplets, organelles that store not only triglycerides and sterols but also free histones H2A, H2Av and H2B. Is there a link between the storage of histones in lipid droplets and the aberrantly structured chromosomes of invadolysin mutants? We have identified a genetic interaction between invadolysin and nonstop, the de-ubiquitinating protease component of the SAGA (Spt-Ada-Gcn5-acetyltransferase) chromatin-remodelling complex. invadolysin and nonstop mutants exhibit phenotypic similarities in terms of chromosome structure in both diploid and polyploid cells. Furthermore, IX-141/not1 transheterozygous animals accumulate mono-ubiquitinated histone H2B (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount immunostaining of IX-141/not1 transheterozygous salivary glands revealed that ubH2B accumulates surprisingly in the cytoplasm, rather than the nucleus. Over-expression of the Bre1 ubiquitin ligase phenocopies the effects of mutating either the invadolysin or nonstop genes. Intriguingly, nonstop and mutants of other SAGA subunits (gcn5, ada2b and sgf11) all suppress an invadolysin-induced rough eye phenotype. We conclude that the abnormal chromosome phenotype of invadolysin mutants is likely the result of disrupting the histone modification cycle, as accumulation of ubH2B and H3K4me3 is observed. We further suggest that the mislocalization of ubH2B to the cytoplasm has additional consequences on downstream components essential for chromosome behaviour. We therefore propose that invadolysin plays a crucial role in chromosome organization via its interaction with the SAGA complex.

Journal Article Type Article
Acceptance Date Feb 28, 2015
Online Publication Date Mar 16, 2015
Publication Date Apr 20, 2015
Deposit Date Mar 23, 2015
Publicly Available Date Mar 23, 2015
Journal Nucleic Acids Research
Print ISSN 0305-1048
Electronic ISSN 1362-4962
Publisher Oxford University Press
Peer Reviewed Peer Reviewed
Volume 43
Issue 7
Pages 3546-3562
Keywords Genetics
Public URL
Publisher URL
Contract Date Mar 23, 2015


nar.gkv211.full.pdf (9.1 Mb)

Publisher Licence URL

Copyright Statement
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited

You might also like

Downloadable Citations