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ORCID

https://orcid.org/0000-0001-8177-8487

Access Type

Open Access Thesis

Document Type

thesis

Degree Program

Animal Science

Degree Type

Master of Science (M.S.)

Year Degree Awarded

2022

Month Degree Awarded

September

Abstract

TATA-Binding Protein Associated Factors 5, 12, and 13 (TAF5, 12, 13) are components of the transcription preinitiation complex (PIC). The transcription PIC is essential for initiation of the transcription at the majority of loci. The transcription PIC is made up of the RNA polymerase II (RNApII) and six general transcription factors TFIIA, TFIIB, TFIID, TFIIE, TFIIF, and TFIIH. The general transcription factor TFIID is made up of TATA-Binding Protein (TBP) and 13 highly conserved TBP-Associated Factors (TAFs). Some TAFs (TAF5, TAF6, TAF9, TAF10, TAF12) are also members of another complex involved in transcription, SAGA (Spt-Ada-Gcn5 acetyltransferase). We have undertaken a systemic characterization of Taf5, Taf12, and Taf13 homozygous mutants to determine the developmental and molecular phenotype in embryos lacking functional Taf5, Taf12, and Taf13. Breeding heterozygous mice of each Taf knockout does not yield Taf5, Taf12, and Taf13 homozygous null pups, indicating that the homozygous embryos are dying in utero. Our studies reveal that Taf5, Taf12 homozygous null embryos share an earlier lethal phenotype than Taf13 homozygous null embryos, suggesting different roles of Tafs that are members of SAGA in addition to TFIID. Taf5 and Taf12 homozygous null embryos fail to implant and are not recovered at day 7.5 of embryonic development (E7.5) whereas Taf13 homozygous null embryos do reach egg-cylinder stage but are developmentally delayed compared to their littermates at E7.5 and fail to initiate gastrulation. We also show transcriptome similarities and differences across Taf5, Taf12 and Taf13 homozygous null embryos by RNA-seq analysis to better understand if these Tafs are involved in two regulatory complexes versus one.

DOI

https://doi.org/10.7275/30825293

First Advisor

Jesse Mager

Second Advisor

Kimberly Tremblay

Third Advisor

Prabin Dhangada-Majhi

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