TEX10

TEX10 is a chromatin-associated transcriptional co-regulator that operates within the embryonic stem cell pluripotency network and is repurposed as a transcriptional effector in germ cell development and cancer (PMID:25936917, PMID:39988597). In embryonic stem cells it is identified through the Sox2 protein interaction network and is recruited to super-enhancers in a Sox2-dependent manner, where it acts together with Tet1 and the histone acetyltransferase p300 to coordinate histone acetylation and DNA demethylation that sustain pluripotency (PMID:25936917, PMID:26046753). Its occupancy at target promoters is directed by the polycomb group RING finger proteins Pcgf3 and Pcgf5, whose deletion sharply reduces both TEX10 and p300 chromatin binding (PMID:29054931). In germ cell development, Tex10 binds H3K4me3-marked promoters of the Wnt negative regulators Psmd3 and Psmd7 to activate their expression and thereby restrain Wnt signaling; its loss arrests spermatocytes at metaphase I and impairs primordial germ cell-like cell specification (PMID:39988597). In cancer contexts TEX10 functions as a transcriptional amplifier: it physically interacts with the NF-κB subunit RELA to increase its nuclear localization and promoter occupancy in colorectal cancer (PMID:32995120), and it binds STAT3 to promote p300-mediated STAT3 acetylation and transcriptional activity driving hepatocellular carcinoma invasion (PMID:37792308).

1. 2015 High

   Establishing that TEX10 is a functional node of the pluripotency network answered whether it had a defined molecular role, placing it on Sox2-dependent super-enhancers controlling chromatin state.

   Evidence Sox2 interaction network with Co-IP, ChIP, bisulfite sequencing, and shRNA loss-of-function in mouse and human ESCs

   PMID:25936917 PMID:26046753

   Open questions at the time

   • Direct catalytic activity of TEX10 itself not defined; it appears to act as a scaffold/recruiter rather than an enzyme
   • Whether super-enhancer recruitment requires Sox2 binding directly or an intermediary not resolved here
2. 2017 High

   Identifying Pcgf3/5 as recruiters answered how TEX10 and p300 reach target promoters, linking a polycomb-associated module to TEX10 chromatin localization.

   Evidence Mass-spectrometry interactome, Co-IP, ChIP-seq, and CRISPR-Cas9 deletion of Pcgf3/5 with RNA-seq in ESCs

   PMID:29054931

   Open questions at the time

   • Structural basis of the TEX10–Pcgf3/5 interaction unknown
   • Whether the same recruitment logic applies outside ESCs not tested
3. 2018 Medium

   Linking TEX10 to cancer stemness extended its role beyond ESCs, implicating STAT3 signaling in hepatocellular carcinoma.

   Evidence shRNA knockdown with stem-cell marker, drug resistance, and STAT3 pathway readouts

   PMID:30045663

   Open questions at the time

   • STAT3 link inferred from downstream markers without direct interaction data in this study
   • No chromatin occupancy data linking TEX10 to STAT3 targets
4. 2019 Medium

   Connecting TEX10 to Wnt/β-catenin signaling in esophageal carcinoma broadened its pathway repertoire, presaging the Wnt-regulatory role later defined mechanistically in germ cells.

   Evidence Lentiviral shRNA knockdown with proliferation, apoptosis, EMT, and β-catenin Western blot readouts

   PMID:31638260

   Open questions at the time

   • Mechanistic link to Wnt based on downstream markers without interaction or ChIP data
   • Directionality (TEX10 promotes vs. restrains Wnt) differs from germ cell findings, unresolved
5. 2020 High

   Demonstrating a TEX10–RELA interaction answered how TEX10 couples to inflammatory transcription, showing it drives NF-κB nuclear localization and target occupancy in colorectal cancer.

   Evidence shRNA screen, Co-IP, nuclear fractionation, ChIP, and in vitro/in vivo proliferation assays

   PMID:32995120

   Open questions at the time

   • How TEX10 increases RELA nuclear import mechanistically not defined
   • Whether p300 participates in this axis as it does for STAT3 not tested
6. 2023 High

   Defining the TEX10–p300–STAT3 axis provided the direct molecular mechanism behind earlier STAT3 association, showing TEX10 promotes p300-mediated STAT3 acetylation.

   Evidence Reciprocal Co-IP, dual-luciferase reporter, ChIP, p300 siRNA rescue, transwell and xenograft assays

   PMID:37792308

   Open questions at the time

   • Whether TEX10 directly bridges p300 and STAT3 or acts indirectly not structurally resolved
   • Relationship between this acetylation function and the ESC p300 module unexplored
7. 2025 High

   Conditional knockout established TEX10's physiological function in germ cell development, showing it activates Psmd3/Psmd7 at H3K4me3 promoters to restrain Wnt and enable spermatogenesis.

   Evidence Conditional KO mice, dTAG-degron ESCs, bulk/single-cell RNA-seq, chromatin occupancy, and PGCLC differentiation with rescue

   PMID:36865339 PMID:39988597

   Open questions at the time

   • How TEX10 reads or is recruited to H3K4me3-marked promoters not defined
   • Reconciliation of Wnt-restraining (germ cells) versus Wnt-promoting (cancer) roles unresolved

• The intrinsic biochemical activity of TEX10 — whether it possesses any catalytic function or acts purely as a scaffold/recruiter — remains undefined across all contexts.
• No structural model of TEX10 or its complexes
• Mechanism of context-dependent partner selection (Pcgf3/5 vs RELA vs STAT3 vs H3K4me3) unknown