Pluripotency factors regulate the onset of Hox cluster activation in the early embryo

• Published in: Science advances 2022-07, Vol.8 (28), p.eabo3583-eabo3583
• Main Authors: Tiana, María, Lopez-Jimenez, Elena, de Aja, Julio Sainz, Barral, Antonio, Victorino, Jesus, Badia-Careaga, Claudio, Rollan, Isabel, Rouco, Raquel, Santos, Elisa, Sanchez-Iranzo, Hector, Acemel, Rafael D., Torroja, Carlos, Adan, Javier, Andres-Leon, Eduardo, Gomez-Skarmeta, Jose Luis, Giovinazzo, Giovanna, Sanchez-Cabo, Fatima, Manzanares, Miguel
• Format: Article
• Language: English
• Subjects: Biomedicine and Life Sciences; Developmental Biology; Genetics; SciAdv r-articles
• ISSN: 2375-2548; 2375-2548
• DOI: 10.1126/sciadv.abo3583

Pluripotent cells are a transient population of the mammalian embryo dependent on transcription factors, such as OCT4 and NANOG, which maintain pluripotency while suppressing lineage specification. However, these factors are also expressed during early phases of differentiation, and their role in the transition from pluripotency to lineage specification is largely unknown. We found that pluripotency factors play a dual role in regulating key lineage specifiers, initially repressing their expression and later being required for their proper activation. We show that Oct4 is necessary for activation of HoxB genes during differentiation of embryonic stem cells and in the embryo. In addition, we show that the HoxB cluster is coordinately regulated by OCT4 binding sites located at the 3′ end of the cluster. Our results show that core pluripotency factors are not limited to maintaining the precommitted epiblast but are also necessary for the proper deployment of subsequent developmental programs. The role of OCT4 extends beyond pluripotency to regulate in a dual fashion lineage determinants such as the Hox genes.