Reviewer's report
Title:Mapping of HNF4alpha target genes in intestinal epithelial cells
Version: 5Date:13 June 2009
Reviewer: Jean-Noel FREUND
Reviewer's report:
The authors have addressed all the questions that were raised except one which
is highly relevant.
This study concerns the role of HNF4a in intestinal differentiation. All the
experiments using microarrays, ChIP, bandshift assays etc have been performed
in human colon cancer cells. Moreover, 2 of the 3 downstream genes that were
analysed more in detail, are intestine-specific, namely the transcription factor
Cdx2 and the digestive enzyme, threhalase. However, the functional assays on
targets promoters (luciferase assays) have been performed using kidney (COS7)
instead of intestinal cells. Because it is obvious that the function of a transcription
factor is highly dependent on the nuclear context, the authors should perform
transfection assays in intestinal cells. This is even more important for the present
study since the stimulatory effect exerted by HNF4a on 2 downstream targets
(Cdx2 and Cingulin) are quantitatively low, respectively 1.5 and 1.3, as estimated
from the data shown in Figs 2E and 4E.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Reviewer's report
Title:Mapping of HNF4alpha target genes in intestinal epithelial cells
Version: 5Date:13 June 2009
Reviewer: Jean-Noel FREUND
Reviewer's report:
The authors have addressed all the questions that were raised except one which
is highly relevant.
This study concerns the role of HNF4a in intestinal differentiation. All the
experiments using microarrays, ChIP, bandshift assays etc have been performed
in human colon cancer cells. Moreover, 2 of the 3 downstream genes that were
analysed more in detail, are intestine-specific, namely the transcription factor
Cdx2 and the digestive enzyme, threhalase. However, the functional assays on
targets promoters (luciferase assays) have been performed using kidney (COS7)
instead of intestinal cells. Because it is obvious that the function of a transcription
factor is highly dependent on the nuclear context, the authors should perform
transfection assays in intestinal cells. This is even more important for the present
study since the stimulatory effect exerted by HNF4a on 2 downstream targets
(Cdx2 and Cingulin) are quantitatively low, respectively 1.5 and 1.3, as estimated
from the data shown in Figs 2E and 4E.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
Please review this paper.
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Reviewer's report
Title:Mapping of HNF4alpha target genes in intestinal epithelial cells
Version: 5Date:13 June 2009
Reviewer: Jean-Noel FREUND
Reviewer's report:
The authors have addressed all the questions that were raised except one which
is highly relevant.
This study concerns the role of HNF4a in intestinal differentiation. All the
experiments using microarrays, ChIP, bandshift assays etc have been performed
in human colon cancer cells. Moreover, 2 of the 3 downstream genes that were
analysed more in detail, are intestine-specific, namely the transcription factor
Cdx2 and the digestive enzyme, threhalase. However, the functional assays on
targets promoters (luciferase assays) have been performed using kidney (COS7)
instead of intestinal cells. Because it is obvious that the function of a transcription
factor is highly dependent on the nuclear context, the authors should perform
transfection assays in intestinal cells. This is even more important for the present
study since the stimulatory effect exerted by HNF4a on 2 downstream targets
(Cdx2 and Cingulin) are quantitatively low, respectively 1.5 and 1.3, as estimated
from the data shown in Figs 2E and 4E.
Level of interest: An article of importance in its field
Quality of written English: Acceptable
Statistical review: No, the manuscript does not need to be seen by a
statistician.
Declaration of competing interests:
I declare that I have no competing interests
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