Referee 2's review:

**********
N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication, the manuscript has been revised in light of these comments and to address other editorial requirements.
**********

In this manuscript, Kondo and colleagues evaluate the potential role of two K9 H3 specific HMTs SUV39H1 and G9a in cancer. These authors reported in a previous paper overexpression of G9a in hepatocellular carcinoma. Here they use a prostate cancer cell line which expresses high levels of SUV39H1 and G9a to explore the functional consequences of their respective downregulation. Results include identification of a decrease of methylation in K9 (dimethylation for G9a, trimethylation for SUV39H1) as well as a decrease in cell growth. Although the authors fail to identify a specific DNA sequence in which changes in the methylation status of K9 occur, interestingly a specific effect in chromosome instability and centrosome disruption is found in association with G9a downregulation.

This piece of work deserves publication in Plos One. However, I would strongly suggest to address the following issues:
a) Perform ChIPs in G9a KD and SUV39H1 KD in repetitive sequences (ideally, pericentromeric and subtelomeric should be included) to investigate changes in the methylation status of K9 H3.
b) Why do not the authors have tried to generate a double knock down for G9a and SUV39H1. Are the individual effects of HMTs cooperative when they are both depleted? In this experiment, the authors should investigate functional consequences in cell growth, chromosomal defects and specially in the modification sattus of K9 H3 at the different genes that they have studied.
c) It would be nice to see whether reintrodcution of the two HMTs reverts the phenotype (at least partially - unlikely, of course, for aberrant chromosome number)