Invadolysin acts genetically via the SAGA complex to modulate chromosome structure

Nucleic Acids Research
Shubha Gururaja RaoMargarete M S Heck

Abstract

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-14(1)/not(1) transheterozygous animals accumulate mono-ubiquitinated histone H2B (ubH2B) and histone H3 tri-methylated at lysine 4 (H3K4me3). Whole mount immunostaining of IX-14(1)/not(1) transheterozygous salivary glands revealed that ubH2B accu...Continue Reading

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Citations

Apr 18, 2015·Biochimica Et Biophysica Acta·Michael A Welte
Sep 14, 2016·Biological Chemistry·Ching-Wen ChangMargarete M S Heck
Sep 11, 2020·Biochimica Et Biophysica Acta. Gene Regulatory Mechanisms·Dayanne V Cornelio-ParraRyan D Mohan
Mar 5, 2021·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Alessandra AntonucciRosa Di Paola

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Methods Mentioned

BETA
ubiquitination
electrophoresis
fluorescence microscopy
acetylation
deubiquitination
ChIP
histone ubiquitination

Software Mentioned

SmartCapture
ImageJ

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