B1 SINE-binding ZFP266 impedes reprogramming through suppression of chromatin opening by pioneering factors
Kaemena, D. F.; Yoshihara, M.; Ashmore, J.; Beniazza, M.; Zhao, S.; Bertenstam, M.; Olariu, V.; Katayama, S.; Okita, K.; Tomlinson, S.; Yusa, K.; Kaji, K.
Show abstract
Induced pluripotent stem cell reprogramming is inherently inefficient and understanding the molecular mechanisms underlying this inefficiency holds the key to successfully control cellular identity. Here, we report 16 novel 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 enhanced iPSC generation in several iPSC reprogramming settings, emerging as the most robust roadblock. Further analyses revealed 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 a co-activator domain converted ZFP266 from a reprogramming inhibitor to a potent reprogramming facilitator. This work proposes SINE-KRAB-ZFP interaction to be a critical regulator of chromatin accessibility at enhancers for efficient cellular identity changes and also serves as a resource to further illuminate molecular mechanisms hindering reprogramming.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- A high-resolution map of functional miR-181 response elements in the thymus reveals the role of coding sequence targeting and an alternative seed match 95%
- Rescuing DNMT1 Fails to Fully Reverse the Molecular and Functional Repercussions of Its Loss in Mouse Embryonic Stem Cells 95%
- Recruitment of Homodimeric Proneural Factors by Conserved CAT-CAT E-Boxes Drives Major Epigenetic Reconfiguration in Cortical Neurogenesis 94%
Similar papers in this journal
- Mechano-osmotic signals control chromatin state and fate transitions in pluripotent stem cells 96%
- The nuclear periphery confers repression on H3K9me2-marked genes and transposons to shape cell fate 96%
- Eomes and Brachyury control pluripotency exit and germ layer segregation by changes of chromatin state 95%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.