Epigenomic Remodeling in Huntington’s Disease—Master or Servant?

Round 1

Reviewer 1 Report

The review by Zimmer-Bensch presents the model where epi-genetic changes occurring in Huntington’s disease neurons, contribute to manifestation of the disease. The author focuses on histon and DNA modifications and the molecular mechanisms responsible for these modifications. Interestingly, Zimmer-Bensch underscores the role of long noncoding RNA in these processes, an important aspect which received less attention in the HD field.

The manuscript is well written and a pleasure to read and the subject of epi-generic aspects of HD is of interest to the readers of the journal.

I do not have issues with this manuscript.

Author Response

I thank the reviewer for the positive evaluation. As now points were raised by the reviewer, I have nothing to say here, just: thank you!

Sincerely,

Geraldine Zimmer-Bensch

Reviewer 2 Report

In the line of text number 118, it is necessary to clarify why Bdnf is found with an initial capital letter.

Please re-write lines 165-170 to make the idea clearer.

On line 263, I suggest expanding the information that is called as unpublished or removing this statement
393

I suggest changing the expression concerning the reference 120 seems to be written informally.

Check line 220, and it is not clear because the text is in red.

I suggest rethinking line 393 to make it more concrete and profound.

between line 377 and 408 seems to be a big block of text, I suggest dividing it into paragraphs to make it easier to read and understand

I consider that the discussion should be re-written, concerning the arguments presented in the review, it seems that the document is very descriptive, I suggest further strengthening the debate, especially about the application of targets or therapeutic routes, precisely in line 414 talking about therapeutic targets but not explained in-depth, this conclusion may sound vague.

I also suggest improving the argument described in text line 425

In general terms, I want to congratulate the author of this interesting article; I think that changes should be made focused on improving and facilitating reading the paragraphs.

Additionally, the discussion and conclusions should be strengthened because they may seem to be a weakness of the text.

Author Response

Dear Editor, dear Reviewers,

First of all, I would like thank the reviewers for their overall positive comments and for the critical points raised, which helped to improve the manuscript.

I addressed all comments and points that were raised as described in detail below. All changes in the text are indicated in red.

I hope the manuscript is now suitable for publication in Epigenomes.

Sincerely,

Geraldine Zimmer-Bensch

Point by point answer to Reviewer´s 2 comments

In the line of text number 118, it is necessary to clarify why Bdnf is found with an initial capital letter.

Gene nomenclature is used is according to the Guidelines for Nomenclature of Genes, Genetic Markers, Alleles, and Mutations in Mouse and Rat  (http://www.informatics.jax.org/mgihome/nomen/gene.shtml)

Please re-write lines 165-170 to make the idea clearer.

I thank the reviewer for this remark, and now more explicitly described the issue. This is now found in line 169-172.

On line 263, I suggest expanding the information that is called as unpublished or removing this statement

We have now the respective manuscript prepared for submission and did an upload of the manuscript at BioRives. Now this is provided as reference (line 267).

393

I suggest changing the expression concerning the reference 120 seems to be written informally.

This is now done (line 398).

Check line 220, and it is not clear because the text is in red.

I apologise for this formal mistake, it is corrected now (now in black).

I suggest rethinking line 393 to make it more concrete and profound.

This has been improved (line 396 ff).

between line 377 and 408 seems to be a big block of text, I suggest dividing it into paragraphs to make it easier to read and understand

The text is now split into different text blocks.

I consider that the discussion should be re-written, concerning the arguments presented in the review, it seems that the document is very descriptive, I suggest further strengthening the debate, especially about the application of targets or therapeutic routes, precisely in line 414 talking about therapeutic targets but not explained in-depth, this conclusion may sound vague.

I also suggest improving the argument described in text line 425

In general terms, I want to congratulate the author of this interesting article; I think that changes should be made focused on improving and facilitating reading the paragraphs.

Additionally, the discussion and conclusions should be strengthened because they may seem to be a weakness of the text.

As suggested by the reviewer the discussion/conclusion is re-written and strengthened (line 422ff).

Round 2

Reviewer 2 Report

This article is an excellent tool for understanding epigenetic phenomena in Huntington's disease; it is a very in-depth and accurate comprehensive review of the subject.

We wish to congratulate the author on making all the changes and accepting our suggestions very efficiently.

We think this article will become a benchmark for delving into pathophysiology under construction.