Decision letter

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Non-canonical TAF complexes regulate active promoters in human embryonic stem cells

Decision letter[highwire:doi]: 
Jim Kadonaga, Reviewing editor, University of California, United States

eLife posts the editorial decision letter and author response on a selection of the published articles (subject to the approval of the authors). An edited version of the letter sent to the authors after peer review is shown, indicating the substantive concerns or comments; minor concerns are not usually shown. Reviewers have the opportunity to discuss the decision before the letter is sent (see review process). Similarly, the author response typically shows only responses to the major concerns raised by the reviewers.

Thank you for choosing to send your work entitled “Non-canonical TAF Complexes Regulate Active Promoters in Human Embryonic Stem Cells” for consideration at eLife. Your article has been evaluated by a Senior Editor and 3 reviewers, two of whom are members of eLife's Board of Reviewing Editors. The following individuals responsible for the peer review of your submission want to reveal their identity: Jim Kadonaga; Danny Reinberg.

The Reviewing Editor and two other reviewers discussed their comments before we reached this decision, and the Reviewing Editor has assembled the following comments based on the reviewers' reports. Our goal is to provide the essential revision requirements as a single set of instructions, so that you have a clear view of the revisions that are necessary for us to publish your work.

In this study, the authors investigated the function of the TAFs (TBP-associated factors) in human embryonic stem cells (hESCs). The conventional/canonical TFIID complex comprises TBP and about 14 TAF subunits. In this work, it was found that TAFs 2, 3, 5, 6, 7, and 11 - but not TAFs 1, 4, 8, 9, 10, 12, and 13 - are expressed in hESCs, and that TAFs 2, 6, 7, and 11 appear to form a novel complex with TBP. By ChIP analysis, two classes of transcriptionally active genes were identified in hESCs. Class I genes are regulated by TAFs 3 and 5, whereas Class II genes are regulated by all six TAFs in hESCs. RNAi depletion of TAF 2, 3, 5, 6, 7, or 11 as well as overexpression of TAF1 caused a decrease in pluripotency. These findings suggest that the proper regulation of TAFs is important for the maintenance of hESCs.

These results reveal that a subset of the pol II TAFs are expressed in hESCs, and that the specific expression of these TAFs is important for the maintenance of pluripotency. The analysis was rigorous, comprehensive, and convincing. The findings are novel, and of high impact and general interest. This work will be appropriate for publication in eLife if the following points are suitably addressed.

1. Fig. 5. Does the knockdown of one TAF affect the occupancy of other TAFs and RNA pol II at the genes analyzed? If such information is available, it would be a useful addition to the paper.

2. Fig. 6E. The range of the Y axis should be from 0 to 100 percent. This would give a better perspective on the data.

3. Fig. 6F. The range of the Y axis should be from 0.0 to 1.0. The authors should also explain what criteria were used to determine whether or not a gene has alternate promoters.