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- Kaemena, DF, et al.
(författare)
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B1 SINE-binding ZFP266 impedes mouse iPSC generation through suppression of chromatin opening mediated by reprogramming factors
- 2023
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 14:1, s. 488-
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Tidskriftsartikel (refereegranskat)abstract
- Induced pluripotent stem cell (iPSC) reprogramming is inefficient and understanding the molecular mechanisms underlying this inefficiency holds the key to successfully control cellular identity. Here, we report 24 reprogramming roadblock genes identified by CRISPR/Cas9-mediated genome-wide knockout (KO) screening. Of these, depletion of the predicted KRAB zinc finger protein (KRAB-ZFP) Zfp266 strongly and consistently enhances murine iPSC generation in several reprogramming settings, emerging as the most robust roadblock. We show that ZFP266 binds Short Interspersed Nuclear Elements (SINEs) adjacent to binding sites of pioneering factors, OCT4 (POU5F1), SOX2, and KLF4, and impedes chromatin opening. Replacing the KRAB co-suppressor with co-activator domains converts ZFP266 from an inhibitor to a potent facilitator of iPSC reprogramming. We propose that the SINE-KRAB-ZFP interaction is a critical regulator of chromatin accessibility at regulatory elements required for efficient cellular identity changes. In addition, this work serves as a resource to further illuminate molecular mechanisms hindering reprogramming.
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- Iwama, K, et al.
(författare)
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Max-stretch reduction for tree spanners
- 2005
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Ingår i: Algorithms and Data Structures / Lecture Notes in Computer Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783540281016 ; 3608, s. 122-133
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Konferensbidrag (refereegranskat)abstract
- A tree t-spanner T of a graph G is a spanning tree of G whose max-stretch is t, i.e., the distance between any two vertices in T is at most t times their distance in G. If G has a tree t-spanner but not a tree (t - 1)-spanner, then G is said to have max-stretch of t. In this paper, we study the Max-Stretch Reduction Problem: for an unweighted graph G = (V, E), find a set of edges not in E originally whose insertion into G can decrease the max-stretch of G. Our results are as follows: (i) For a ring graph, we give a linear-time algorithm which inserts k edges improving the max-stretch optimally. (ii) For a grid graph, we give a nearly optimal max-stretch reduction algorithm which preserves the structure of the grid. (iii) In the general case, we show that it is NP-hard to decide, for a given graph G and its spanning tree of max-stretch t, whether or not one-edge insertion can decrease the max-stretch to t- 1. (iv) Finally, we show that the max-stretch of an arbitrary graph on n vertices can be reduced to s' >= 2 by inserting O(n/s') edges, which can be determined in linear time, and observe that this number of edges is optimal up to a constant.
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