Abstract
Chd1 is a chromatin remodeler that is involved in nucleosome positioning and transcription. Deletion of CHD1 is a frequent event in prostate cancer. The Structural Maintenance of Chromosome (SMC) complex cohesin mediates long-range chromatin interactions and is involved in maintaining genome stability. We provide new evidence that Chd1 is a regulator of cohesin. In the yeast S. cerevisiae, Chd1 is not essential for viability. We show that deletion of the gene leads to a defect in sister chromatid cohesion and in chromosome morphology. Chl1 is a non-essential DNA helicase that has been shown to regulate cohesin loading. Surprisingly, co-deletion of CHD1 and CHL1 results in an additive cohesion defect but partial suppression of the chromosome structure phenotype. We found that the cohesin regulator Pds5 is overexpressed when Chd1 and Chl1 are deleted. However, Pds5 expression is reduced to wild type levels when both genes are deleted. Finally, we show a correlation in the expression of CHD1 and cohesin genes in prostate cancer patients. Furthermore, we show that overexpression of cohesin subunits is correlated with the aggressiveness of the tumor. The biological roles of the interplay between Chd1, Chl1 and SMCs are discussed.
| Original language | English |
|---|---|
| Article number | 8929 |
| Journal | Scientific Reports |
| Volume | 9 |
| Issue number | 1 |
| DOIs | |
| State | Published - 1 Dec 2019 |
Bibliographical note
Funding Information:We thank Jennifer Gerton for providing yeast strains. Vinny Guacci and Doug Koshland for antibodies. We also thank members of the Onn lab for their support and Dr. Alessandro Gorohovski (MFM Lab) for the validation of our networks analysis. This work was supported by the Israel Cancer Association Grant 20170111 (IO), The Jerome Lejeune Foundation Grant 1146-OI2013_A (IO) and the Israel Science Foundation Grant 1099/16 (IO). IO and MFM are members of the Dangoor Personal Medicine Institute at the Bar-Ilan University.
Publisher Copyright:
© 2019, The Author(s).
