TY - JOUR
T1 - Cell-type-specific functionality encoded within the intrinsically disordered regions of OCT4
AU - Ozkan, Burak
AU - de Anda, Mitzy Rios
AU - Hall-Ponsele, Elisa
AU - Migueles, Maria Rosa Portero
AU - Alshaikh, Amani
AU - Hanzevacki, Marta
AU - Naama, Moriyah
AU - Furlong, Katharine
AU - Roberts, Gareth A.
AU - Beniazza, Meryam
AU - Huynh, My Linh
AU - O’Dwyer, Michael R.
AU - Yiakoumi, Sonia
AU - Spanos, Christos
AU - Yassen, Hazar
AU - Kaji, Keisuke
AU - Niwa, Hitoshi
AU - Buganim, Yosef
AU - Lowell, Sally
AU - Soufi, Abdenour
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - The cell-type-specific function of transcription factors (TFs) is crucial for determining cellular identity. However, it is unclear how a single TF can function specifically in different cell types. Here, we define the molecular features that enable OCT4 to reprogram somatic cells into pluripotent or trophoblast stem cells, maintain the self-renewal of embryonic stem cells (ESCs), and drive lineage commitment during early embryonic development. Embedded within the intrinsically disordered regions (IDRs) of OCT4, we uncover short linear peptides that are essential for reprogramming (SLiPERs) but dispensable for ESC self-renewal. SLiPERs adopt a quasi-ordered state and, during reprogramming, recruit a unique set of proteins to closed chromatin that are unnecessary for ESC self-renewal. Interestingly, SLiPERs are essential for embryos to develop beyond late gastrulation. Removing SLiPERs leads to aberrant OCT4 binding, derailing the regular transition of ESCs out of pluripotency. Our findings identify modules within IDRs that contribute to the functional versatility and specificity of TFs.
AB - The cell-type-specific function of transcription factors (TFs) is crucial for determining cellular identity. However, it is unclear how a single TF can function specifically in different cell types. Here, we define the molecular features that enable OCT4 to reprogram somatic cells into pluripotent or trophoblast stem cells, maintain the self-renewal of embryonic stem cells (ESCs), and drive lineage commitment during early embryonic development. Embedded within the intrinsically disordered regions (IDRs) of OCT4, we uncover short linear peptides that are essential for reprogramming (SLiPERs) but dispensable for ESC self-renewal. SLiPERs adopt a quasi-ordered state and, during reprogramming, recruit a unique set of proteins to closed chromatin that are unnecessary for ESC self-renewal. Interestingly, SLiPERs are essential for embryos to develop beyond late gastrulation. Removing SLiPERs leads to aberrant OCT4 binding, derailing the regular transition of ESCs out of pluripotency. Our findings identify modules within IDRs that contribute to the functional versatility and specificity of TFs.
UR - https://www.scopus.com/pages/publications/105017765279
U2 - 10.1038/s41467-025-63806-3
DO - 10.1038/s41467-025-63806-3
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C2 - 41028752
AN - SCOPUS:105017765279
SN - 2041-1723
VL - 16
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 8647
ER -