Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein.

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Publication Type Journal Article
School or College College of Science; School of Medicine
Department Oncological Sciences; Biology; Human Genetics
Program Institute of Human Genetics; Howard Hughes Medical Institute (HHMI)
Creator Capecchi, Mario R.
Other Author Schmidt, Edward E.; Bondareva, Alla A.; Radke, Jay R.
Title Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein.
Date 2003-02-21
Description The 180-amino acid core of the TATA-binding protein (TBPcore) is conserved from Archae bacteria to man. Vertebrate TBPs contain, in addition, a large and highly conserved N-terminal region that is not found in other phyla. We have generated a line of mice in which the tbp allele is replaced with a version, tbp(Delta N), which lacks 111 of 135 N-terminal amino acid residues. Most tbp(Delta N/Delta N) fetuses die in midgestation. To test whether a disruption of general cellular processes contributed to this fetal loss, primary fibroblast cultures were established from +/+, Delta N/+, and Delta N/Delta N fetuses. The cultures exhibited no genotype-dependent differences in proliferation or in expression of the proliferative markers dihydrofolate reductase (DHFR) mRNA (S phase-specific) and cdc25B mRNA (G(2)-specific). The mutation had no effect on transcription initiation site fidelity by either RNA polymerase II (pol II) or pol III. Moreover, the mutation did not cause differences in levels of U6 RNA, a pol III-dependent component of the splicing machinery, in mRNA splicing efficiency, in expression of housekeeping genes from either TATA-containing or TATA-less promoters, or in global gene expression. Our results indicated that general eukaryotic cell functions are unaffected by deletion of these vertebrate-specific sequences from TBP. Thus, all activities of this polypeptide domain must either be compensated for by redundant activities or be restricted to situations that are not represented by primary fibroblasts.
Type Text
Publisher American Society for Biochemistry and Molecular Biology (ASBMB)
Volume 278
Issue 8
First Page 6168
Last Page 6174
Subject Mice, Knockout; Cells, Cultured; Fibroblasts; Embryo
Subject MESH Protein Biosynthesis; Transcription, Genetic; Gene Expression Regulation
Language eng
Bibliographic Citation J Biol Chem. 2003 Feb 21;278(8):6168-74. Epub 2002 Dec 5: Schmidt EE, Bondereva AA, Radke JR, Capecchi MR. Fundamental cellular processes do not require vertebrate-specific sequences within the TATA-binding protein.Retrieved on September 15.2006 from http://www.jbc.org/cgi/content/full/278/8/6168.
Rights Management Copyright 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Format Medium application/pdf
Identifier ir-main,410
ARK ark:/87278/s6qz2v4k
Setname ir_uspace
Date Created 2012-06-13
Date Modified 2012-06-13
ID 702934
Reference URL https://collections.lib.utah.edu/ark:/87278/s6qz2v4k
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