Abstract
The general transcription initiation factor TFIID and its interactors play critical roles in regulating the transcription from both naked and chromatin DNA. We have isolated a novel TFIID interactor that we denoted as CCG1/TAF(II)250-interacting factor B (CIB). We show here that CIB activates transcription. To further understand the function of this protein, we determined its crystal structure at 2.2-Angstroms resolution. The tertiary structure of CIB reveals an alpha/beta-hydrolase fold that resembles structures in the prokaryotic alpha/beta-hydrolase family proteins. It is not similar in structure or primary sequence to any eukaryotic transcription or chromatin factors that have been reported to date. CIB possesses a conserved catalytic triad that is found in other alpha/beta-hydrolases, and our in vitro studies confirmed that it bears hydrolase activity. However, CIB differs from other alpha/beta-hydrolases in that it lacks a binding site excursion, which facilitates the substrate selectivity of the other alpha/beta-hydrolases. Further functional characterization of CIB based on its tertiary structure and through biochemical studies may provide novel insights into the mechanisms that regulate eukaryotic transcription.
Highlights
Eukaryotic gene expression is mainly regulated at the level of transcription initiation from chromatin templates [1,2,3]
When we isolated and characterized various TFIID interactors, we found that one of the TBP-associated factor (TAF) interactors is a MOZ-Ybf2/Sas3-Sas2-Tip60 (MYST)-type histone acetyltransferase (HAT) denoted as Tip60 (Tat-interactive protein 60) (29 –32) and that one of the CCG1 interactors is a histone chaperone denoted as CIA (CCG1-interacting factor A) [33,34,35,36,37]
Northern blot hybridization analysis shows that CCG1/TAFII250-interacting factor B (CIB) mRNA is expressed in almost all human tissues (Fig. 2B), which indicates that CIB is ubiquitously expressed
Summary
Crystallographic analyses have revealed that there are multiple histone-fold pairs in TFIID [19, 20]. When we isolated and characterized various TFIID interactors, we found that one of the TAF interactors is a MOZ-Ybf2/Sas3-Sas2-Tip (MYST)-type HAT denoted as Tip (Tat-interactive protein 60) (29 –32) and that one of the CCG1 interactors is a histone chaperone denoted as CIA (CCG1-interacting factor A) [33,34,35,36,37]. These proteins are highly conserved among various species, and they regulate several nuclear events, including DNA replication, DNA repair, transcription, silencing, and apoptosis, which indicates that they play important roles in regulating chromatin. The presented structure shows a fold that is similar to one found in prokaryotic ␣/-hydrolase family proteins, even though these proteins show very little sequence homology with CIB
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