Details

Autor(en) / Beteiligte

• He, Xinjian Doris
• Phillips, Shelby
• Hioki, Kaito
• Majhi, Prabin Dhangada
• Babbitt, Courtney
• Tremblay, Kimberly D.
• Pobezinsky, Leonid A.
• Mager, Jesse

Titel

TATA-binding associated factors have distinct roles during early mammalian development

Ist Teil von

• Developmental biology, 2024-07, Vol.511, p.53-62

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2024

Quelle

MEDLINE

Beschreibungen/Notizen

• Early embryonic development is a finely orchestrated process that requires precise regulation of gene expression coordinated with morphogenetic events. TATA-box binding protein-associated factors (TAFs), integral components of transcription initiation coactivators like TFIID and SAGA, play a crucial role in this intricate process. Here we show that disruptions in TAF5, TAF12 and TAF13 individually lead to embryonic lethality in the mouse, resulting in overlapping yet distinct phenotypes. Taf5 and Taf12 mutant embryos exhibited a failure to implant post-blastocyst formation, and Taf5 mutants have aberrant lineage specification within the inner cell mass. In contrast, Taf13 mutant embryos successfully implant and form egg-cylinder stages but fail to initiate gastrulation. Strikingly, we observed a depletion of pluripotency factors in TAF13-deficient embryos, including OCT4, NANOG and SOX2, highlighting an indispensable role of TAF13 in maintaining pluripotency. Transcriptomic analysis revealed distinct gene targets affected by the loss of TAF5, TAF12 and TAF13. Thus, we propose that TAF5, TAF12 and TAF13 convey locus specificity to the TFIID complex throughout the mouse genome. [Display omitted] •Taf5 and Taf12 mutant embryos form blastocysts but fail to implant.•Taf5 mutants exhibit aberrant lineage specification within the inner cell mass.•Taf13 mutant embryos fail to initiate gastrulation.•Taf13 mutant embryos are missing pluripotency factors OCT4, NANOG and SOX2.•Transcriptomes suggest each TAF (−5, −12, −13) confers unique locus specificity.