Requirement for TAF<sub>II</sub>250 Acetyltransferase Activity in Cell Cycle Progression

doi:10.1128/mcb.20.24.9434-9434.2000

Cited by 22 publications

(45 citation statements)

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“…Most importantly, the DALI search revealed no obvious structural similarities between yTAF1 and any known HATs. It has previously been proposed that TAF1 harbors putative Gly-X-Gly motifs, which mediate acetyl Co-A substrate recognition that is required for HAT activity (9,23). Visual inspection reveals, however, that these motifs are actually located at different positions in yeast (in the loop connecting strands β7 and β8 in the triple barrel region) and human (near the end of helix α9 in the cradle region) TAF1 sequences (Fig.…”

Section: Resultsmentioning

confidence: 99%

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Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Bhattacharya

Lou

Hwang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Transcription factor II D (TFIID) is a multiprotein complex that nucleates formation of the basal transcription machinery. TATA binding protein-associated factors 1 and 7 (TAF1 and TAF7), two subunits of TFIID, are integral to the regulation of eukaryotic transcription initiation and play key roles in preinitiation complex (PIC) assembly. Current models suggest that TAF7 acts as a dissociable inhibitor of TAF1 histone acetyltransferase activity and that this event ensures appropriate assembly of the RNA polymerase IImediated PIC before transcriptional initiation. Here, we report the 3D structure of a complex of yeast TAF1 with TAF7 at 2.9 Å resolution. The structure displays novel architecture and is characterized by a large predominantly hydrophobic heterodimer interface and extensive cofolding of TAF subunits. There are no obvious similarities between TAF1 and known histone acetyltransferases. Instead, the surface of the TAF1-TAF7 complex contains two prominent conserved surface pockets, one of which binds selectively to an inhibitory trimethylated histone H3 mark on Lys27 in a manner that is also regulated by phosphorylation at the neighboring H3 serine. Our findings could point toward novel roles for the TAF1-TAF7 complex in regulation of PIC assembly via reading epigenetic histone marks.initiation complex | protein structure | protein-protein interaction | X-ray crystallography T he general transcription factor II D (TFIID) plays a central role in recognition of the core promoter element and mediates accurate transcription initiation by RNA Polymerase (Pol) II for a large class of genes. TFIID nucleates the formation of the preinitiation complex (PIC) at the transcriptional start site by recruiting other general transcription factors (TFII-A, -B, -E, -F, and -H), along with RNA Pol II. TFIID is assembled in a stepwise manner, with a symmetric TFIID core complex recruited first, followed by further recruitment of additional TATA binding protein (TBP)-associated factors (TAFs) to form the complete asymmetric holo-TFIID complex (1). This megadalton-sized multiprotein assembly, comprised of TBP and 13 evolutionary conserved TAFs (2), is organized into a trilobed structure (3) and undergoes striking rearrangements upon binding to TFIIA and DNA (4). TAF subunits serve multiple functions within the TFIID holocomplex. In addition to TBP, TAF1, TAF2, TAF6, and TAF9 are also involved in recognition of DNA initiator and promoter elements. Moreover, TFIID can behave as an epigenetic effector, capable of recognizing posttranslational histone modifications associated with activated transcription. Eukaryotic TAF1 contains a double bromodomain that recognizes acetylated histones, and TAF3 contains a plant homeo domain (PHD) that binds to histone H3 methylated at lysine 4 (5, 6). In addition to roles in basal transcription, TFIID is also associated with diseases. Overexpression of TAF1, which acts as a specific coactivator of androgen receptor, is related to the progression of human prostate cancer (7). Additionally, altera...

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Section: Resultsmentioning

confidence: 99%

“…Interestingly, yTAF1Gly561, a conserved residue that is subject to a temperature-sensitive (ts) mutation (Gly561Asp) that interferes with cell cycle progression in cultured eukaryotic cells (23,24), is located next to aromatic residues that form the pocket 2 wall (Fig. S9A).…”

Section: Resultsmentioning

confidence: 99%

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Bhattacharya

Lou

Hwang

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…These data are consistent with previous studies carried out in the ts13 variant hamster cell line. The ts13 variant hamster cell line contains a temperature-sensitive missense variant in the DUF3591domain of TAF1 which causes G1/S phase cell cycle arrest and transcriptional down regulation of CCND1 but not FOS (MIM: 164810) [39,40]. Additionally, loss of CCND1 reportedly impairs cerebellar development [41].…”

Section: Discussionmentioning

confidence: 99%

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome

et al. 2018

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We investigated the genome of a 5-year old male who presented with global developmental delay (motor, cognitive, and speech), hypotonia, possibly ataxia, and cerebellar hypoplasia of unknown origin. Whole genome sequencing and mRNA-sequencing were performed on a family containing an affected proband, his unaffected parents and maternal grandfather. To explore the molecular and functional consequences of the variant, we performed cell proliferation assays, qRT-PCR array, immunoblotting, calcium imaging, and neurite outgrowth experiments in SH-SY5Y neuroblastoma cells to compare the properties of the wild type TAF1, deletion of TAF1, and TAF1 variant p.Ser1600Gly samples. The whole genome data identified several gene variants. However, the genome sequence data failed to implicate a candidate gene as many of the variants were of unknown significance. By combining genome sequence data with transcriptomic data, a probable candidate variant, p.Ser1600Gly, emerged in TAF1. Moreover, the RNA-seq data revealed a 90:10 extremely skewed X-chromosome inactivation in the mother. Our results show that neuronal ion channel genes were differentially expressed between TAF1 deletion and TAF1 variant p.Ser1600Gly cells, when compared to their respective controls, and that the TAF1 variant may impair neuronal differentiation and cell proliferation. Taken together, our data suggests that this novel variant in TAF1 plays a key role in the development of a recently described X-linked syndrome, TAF1 intellectual disability syndrome, and further extends our knowledge of a potential link between TAF1 deficiency and defects in neuronal cell function.

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“…The HAT activity of TAF II 250 is temperature sensitive in ts13 cells (Dunphy et al, 2000), suggesting that the acetylation of histones and possibly of other target proteins by TAF II 250 plays a role in TAF II 250-dependent gene expression (Dunphy et al, 2000). The results presented so far raised the question of whether BMyb is acetylated by TAF II 250.…”

Section: Coimmunoprecipitation Of Taf II 250 and B-mybmentioning

confidence: 87%

“…The ts13 hamster cell line harbors a single point mutation in the gene encoding TAF II 250, which renders the acetyltransferase activity of TAF II 250 temperature-sensitive (Hisatake et al, 1993;Dunphy et al, 2000). When ts13 cells are grown at the nonpermissive temperature, they arrest in the G1 phase of the cell cycle and undergo apoptosis.…”

Section: Introductionmentioning

confidence: 99%

Transactivation mediated by B-Myb is dependent on TAFII250

Bartusel

Klempnauer

2003

Oncogene

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B-Myb is a highly conserved member of the Myb family of transcription factors, which has been implicated in cell cycle regulation. B-Myb is expressed in most proliferating cells and its activity is highly regulated around the G1/Sphase border of the cell cycle. It is generally assumed that B-Myb regulates the expression of genes that are crucial for cell proliferation; however, the identity of these genes, the molecular mechanisms by which B-Myb stimulates their expression and the involvement of other proteins have not been sufficiently clarified. We have employed the hamster cell line ts13 as a tool to demonstrate a functional link between B-Myb and the coactivator TAF II 250, a key component of the transcriptional machinery which itself is essential for cell proliferation. ts13 cells express a pointmutated version of TAF II 250 whose intrinsic histone acetyl transferase activity is temperature sensitive. Transactivation of Myb-responsive reporter genes by BMyb is temperature-dependent in ts13 cells but not in ts13 cells, which have been rescued by transfection with an expression vector for wild-type TAF II 250. Furthermore, B-Myb and TAF II 250 can be coprecipitated, suggesting that both proteins are present in a complex. The formation of this complex is dependent on the DNA-binding domain of B-Myb and not on its transactivation domain. Taken together, these observations provide the first evidence that the coactivator TAF II 250 is involved in the activation of Myb responsive promoters by B-Myb. The finding that BMyb transactivation is dependent on a key coactivator involved in cell cycle control is consistent with and strengthens the idea that B-Myb plays a crucial role as a transcription factor in proliferating cells.

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Requirement for TAF_II250 Acetyltransferase Activity in Cell Cycle Progression

Cited by 22 publications

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Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome

Transactivation mediated by B-Myb is dependent on TAFII250

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Requirement for TAFII250 Acetyltransferase Activity in Cell Cycle Progression

Cited by 22 publications

References 0 publications

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

Structural and functional insight into TAF1–TAF7, a subcomplex of transcription factor II D

A novel variant in TAF1 affects gene expression and is associated with X-linked TAF1 intellectual disability syndrome

Transactivation mediated by B-Myb is dependent on TAFII250

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Requirement for TAF_II250 Acetyltransferase Activity in Cell Cycle Progression