How Chromatin Motor Complexes Influence the Nuclear Architecture: A Review of Chromatin Organization, Cohesins, and Condensins with a Focus on C. elegans
![](/bundles/mdpisciprofileslink/img/unknown-user.png)
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript “How chromatin motor complexes influence the nuclear architecture: a review of chromatin organization, cohesins, and condensins with a focus on C. elegans” by Chawla and Csankovszki is a review of the recent findings of cohesin and condensin complex composition across species and their role in global genome organization. At the end, the authors delve deep into the role of condensin I^DC in the curious case of X chromosome dosage compensation in hermaphrodite worms. This case is particularly interesting, as none of the C. elegans autosomes display discrete TADs, dosage compensated X chromosomes do. This allows for a unique and tangible set of chromosomes that can be studies to understand how TADs are formed and what their roles are in gene regulation. Overall, it is a well written review that is pleasant to read, and which will be informative to a reader new to the field. This reviewer only has a few comments.
1. Section 2 can be improved by briefly discussing the mechanistic operations of cohesin and condensin complexes extruding DNA at the single molecule level as shown by Cees Dekker and others. This will provide a strong setting to later discuss how dosage compensation might happen in C. elegans.
2. A figure explaining DCC would be very helpful.
3. To Figure 2, it would be informative and helpful is functional implications are added to the figure to help the reader better understand what the importance of the various domains of SMC proteins are.
4. Although commonly used, the term higher eukaryote is a misnomer. All species have evolved the same amount of time. Some are single cell species, others are multicellular, again others switch between these two states. This reviewer advises to avoid using ranking term to describe lifeforms.
5. Similarly, to the previous point, prokaryotes is a commonly used term. It is generally accepted that eukaryotes have evolved from archaea and that archaea have evolved from bacteria. Grouping bacteria and archaea into one group would be inaccurate. It would be akin to grouping fungi and plants together against animals. As this manuscript touches on the evolution of SMC proteins, an evolutionary faithful description would be appreciated.
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 2 Report
Comments and Suggestions for AuthorsThe authors explored one of the most critical issues in genome biology, providing significant information in this paper. However, the structures need to be significantly edited.
Major Comments:
- 1. While the authors focused on C. elegans, the introduction and several initial sections lack emphasis on C. elegans. This may leave readers questioning the paper's focus. I recommend enhancing the discussion of C. elegans in the introduction and initial sections, highlighting its features and explaining why studying this case is essential. Additionally, introduce the features of C. elegans compartments and TADs in the introduction instead of emphasizing mammalian genome organization. The focus on C. elegans SMCs is also unclear in sections 2 and 3.
2. The article should be more structured, It's awkward to introduce the common SMC structure in Fig. 2 within the condensin section; clarify this when the first SMC is introduced. Introduce SMC structure (Fig. 2) when cohesin is discussed. Define 'Kleisin' earlier, as mentioned in the previous chapter.
3. In section 3, clarify the involvement of condensin I DC in dosage compensation, ensuring a natural flow of logic to maintain reader interest. The section on how condensin I DC is involved in dosage compensation needs revision to ensure a natural flow of logic. As the paper's title focuses on cohesin and condensin, it's crucial to highlight how condensin I DC is involved in dosage compensation.
Minor Comments:
- 1. Briefly explain the role of Smc5/6 in C. elegans after introducing them in line 149.
- 2. Omit the comparison between HWAK and KITE in lines 185-195 since the focus is on condensin and cohesin, and no KITE proteins are shown in figures or tables. Develop a more concrete storyline to capture readers' interest.
- 3. Change "other eukaryotes" in line 284 to "other some species" or "mammalian" as yeast and plants also lack CTCF. Include this information in Table 1.
- 4. Provide more explanation on the molecular mechanism by which rex sites could be analogous to CTCF-binding sites. Suggest potential CTCF-like proteins in rex sites of C. elegans.
- 5. Correct typos: omit the period in line 14, and correct "homeostasiss" to "homeostasis" in line 33.
Comments on the Quality of English Language
Minor issue
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Reviewer 3 Report
Comments and Suggestions for AuthorsB. Chawla and G. Csankovszki's review provides a comprehensive look at chromatin organization in eukaryotic nuclei, highlighting the roles of chromatin motor complexes, cohesin, and condensin, with a specific focus on the model organism C. elegans.
The review is very well-written overall. Although the title and abstract imply a significant focus on C. elegans in the review, this organism is only extensively discussed in the latter part. The initial general introduction to chromatin organization relies heavily on data from mammals and yeast, areas where numerous similar reviews already exist.
To enhance the distinct focus of their review, I recommend that the authors make slight adjustments to the organization, emphasizing both the similarities and differences in chromatin organization in C. elegans throughout the entirety of their review.
Specifically, I recommend offering additional insights into the specificities of TAD organization along C. elegans autosomes, as outlined by the Meyer and Ahringer labs (e.g., doi: 10.1101/gr.275669.121), in the TAD paragraph beginning at line 60.
Similarly, the authors should include the discussion on the absence of CTCF in C. elegans in section 2 (from line 100).
Other comments:
- The sentence “In fission yeast, Rec8 replaces Scc1 in cohesin, while either Rec11 or Psc3 replace Scc3” is wrong: Psc3 is the fission yeast Scc3, and Rec11 only partially replaces Psc3/Scc3 during meiosis (line 137/8).
- Table 1 is incomplete (missing meiotic cohesin subunits for S. cerevisiae (Rec8) and Xenopus (SMC1b, …)
- Maybe add DOI: 10.1126/science.abm4012 for a structure-based model for loop extrusion rather than ref 67 (line 178).
- line 190 (ref 69): The sentence “Instead, the HEAT-repeat domain containing proteins in present day eukaryotic condensins and cohesins are assumed to evolved uniquely to replace Kites in the condensin inherited from the last common eukaryotic ancestor” is a bit misleading since ref 69 speculates that the evolution of HEAT domains may precede the LECA (last eukaryotic common ancestor).
- Line 239: Is citation 40 accurate for the Rabl configuration? Ref 80 appears to be a more suitable reference in this context.
- I suggest removing the mention of “one model organism” regarding holocentric chromosomes (line 251) since there are many species with holocentric chromosomes, and some of these species are also used as non-canonical model organisms.
- Ref 89 is wrong in line 267: here, the authors apparently refer to a sentence in the introduction of [89] that in turn refers to refs 23, 30, and 31 of [89].
- insert missing space in line 291 (proteins [93-96])
- using MIX-1 for C. elegans Smc2 is inconsistent (line 341)
- … when SDC-2 expression begins in embryos [131] (line 355): maybe add “ in hermaphrodite embryos” since the DCC is not loaded in male embryos.
- References: spaces are missing in the titles of some references, such as 157 and 160
Author Response
Please see the attachment.
Author Response File: Author Response.docx
Round 2
Reviewer 2 Report
Comments and Suggestions for AuthorsNo other comments.