VEZF1 facilitates pluripotency exit by regulating developmental transcriptional programs and CTCF occupancy

Zfp462 Regulates the Pluripotency of Embryonic Stem Cells by Cooperating with the Core Transcriptional Network.

Distinct regulation of Wnt signaling and EPZ5676 governs human UiPSM reprogramming via the CDX2/T/TBX6 core axis

An ideal in vitro system to study somitogenesis is induced presomitic mesoderm (UiPSM); the regulatory pathways of this system are not well understood. Here, integrated multi-omic and functional analyses were performed to elucidate the roles of Wnt signaling and EPZ5676 in UiPSM reprogramming. The findings showed that the Wnt/β-catenin signaling activation by CHIR is essential to induce UiPSM, which facilitates chromatin remodeling and the activation of major presomitic mesoderm (PSM) transcription factors (TFs). Conversely, EPZ5676 controls when reprogramming occurs and increases the efficiency of reprogramming by controlling chromatin dynamics without dictating cell fate. The TFs CDX2, T (Brachyury), and TBX6 were found to be a central regulatory axis whose functions were partially redundant. Mechanistically, CDX2 directly interacts with the regulatory regions of WNT3A, T, and TBX6, maintaining their chromatin accessibility and transcriptional activity and creating a positive feedback loop of Wnt/β-catenin-dependence. Moreover, the interaction between CDX2, T, and TBX6 with Wnt signaling is reciprocal to establish a stable regulatory network that preserves UiPSM identity and stemness. Taken together, this work shows that Wnt/β-catenin signaling coordinates UiPSM reprogramming and maintenance via the CDX2/T/TBX6 axis, which offers new mechanistic understanding of human mesoderm lineage specification and somatic cell reprogramming.

TUG1 supports mouse two-cell-stage development and ZGA-associated transcription through MAPK8 signaling

It is demonstrated that TUG1, which is highly expressed in tumors, regulates early embryonic development in mice and is transformed from a cancer-specific effector to a critical regulator of the ZGA, raising the possibility that related regulatory principles may operate in other biological contexts.

Polycomb establishes TAD-scale H3K27me3 mega-domains to safeguard neuronal identity

These findings reveal a previously unrecognized role for PRCs in establishing TAD-scale repressive chromatin domains during neuronal maturation, thereby safeguarding neuronal identity from external stimuli through broad silencing of alternative cell fate programs.

TAL1 is indispensable in ETV2-primed human endothelial cell fate determination

It is demonstrated that ETV2 drives the rapid forward programming of human pluripotent stem cells (hPSCs) into endothelial cells (ECs) by direct remodeling of endothelial-specific enhancers and is established as a master gatekeeper of human EC specification.

TRIM28 PRESERVES OVARIAN IDENTITY BY STABILIZING LINEAGE-SPECIFIC TRANSCRIPTION FACTOR HUBS

Maintenance of ovarian cell identity is required throughout life to prevent the activation of the testicular program, but the epigenetic mechanisms underlying this process remain poorly understood. Although TRIM28 is required to prevent granulosa-to-Sertoli transdifferentiation, it can act both as a regulator of H3K9me3-dependent heterochromatin and as a transcriptional activator through its E3 SUMOligase activity. Here, we combined CUT&RUN, ATAC-seq and RNA-seq to define the respective contributions of these activities to maintain ovarian cell identity. Strikingly, only a small fraction of TRIM28-bound regions was associated with H3K9me3. Although Trim28 deletion induced focal H3K9me3 loss, it had limited transcriptional consequences and primarily affected repetitive elements rather than regions controlling testis-determining genes. In contrast, Trim28 loss led to reductions in chromatin accessibility and H3K27ac at regions enriched for ovarian transcription factor (TF) motifs FOXL2, NR5A2, ESR2 and RUNX1. Moreover, TRIM28 was frequently co-localized with these TFs on chromatin, and the accessibility and the SUMOylation at these co-bound regions were reduced by Trim28 deletion. Together, our findings identify TRIM28 as a central organizer of ovarian TF hubs whose predominant function is to preserve granulosa cell identity through stabilization of lineage-specific TFs rather than H3K9me3-dependent heterochromatin. GRAPHICAL ABSTRACT