Structural bioinformatics of the general transcription factor TFIID

Małkowska, Maja; Kokoszyńska, Katarzyna; Rychlewski, Leszek; Wyrwicz, Lucjan

doi:10.1016/j.biochi.2012.10.024

Cited by 25 publications

(21 citation statements)

References 111 publications

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“…48, 49, 50 The TAF2 gene is involved in general transcription processes and is the DNA binding component of the transcription factor II D transcription factor complex. 51 …”

Section: Resultsmentioning

confidence: 99%

Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

et al. 2014

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Genetic and epigenetic (DNA methylation, histone modifications, microRNA expression) crosstalk promotes inactivation of tumor suppressor genes or activation of oncogenes by gene loss/hypermethylation or duplications/hypomethylation, respectively. The 8p11-p12 chromosomal region is a hotspot for genomic aberrations (chromosomal rearrangements, amplifications and deletions) in several cancer forms, including breast carcinoma where amplification has been associated with increased proliferation rates and reduced patient survival. Here, an integrative genomics screen (DNA copy number, transcriptional and DNA methylation profiling) performed in 229 primary invasive breast carcinomas identified substantial coamplification of the 8p11-p12 genomic region and the MYC oncogene (8q24.21), as well as aberrant methylation and transcriptional patterns for several genes spanning the 8q12.1-q24.22 genomic region (ENPP2, FABP5, IMPAD1, NDRG1, PLEKHF2, RRM2B, SQLE, TAF2, TATDN1, TRPS1, VPS13B). Taken together, our findings suggest that MYC activity and aberrant DNA methylation may also have a pivotal role in the aggressive tumor phenotype frequently observed in breast carcinomas harboring 8p11-p12 regional amplification.

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“…48, 49, 50 The TAF2 gene is involved in general transcription processes and is the DNA binding component of the transcription factor II D transcription factor complex. 51 …”

Section: Resultsmentioning

confidence: 99%

Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

et al. 2014

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“…As a result, it was possible to identify the position of a TAF1-TAF7 complex by docking of its crystal structure [25] in the region of contact with downstream DNA. Furthermore, a large segment of TAF2 that shares homology with M1 aminopeptidases [26] could be fitted into the lobe C map adjacent to TAF1-TAF7 using crystal structures [26,27]. Within the remaining unassigned region in lobe C, we identified a HEAT-repeat present in two copies, forming an apparent homodimer that could be readily accommodated by fitting two copies of the TAF6 HEAT-repeat crystal structure from a microsporidium fungi [28] (see Figure 2d for final protein and DNA elements assignment).…”

Section: Progress Dealing With Conformational Heterogeneity: Tfiid Bimentioning

confidence: 99%

Cryo-EM in the study of challenging systems: the human transcription pre-initiation complex

Nogales

Louder

2016

Current Opinion in Structural Biology

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Single particle cryo-Electron Microscopy (cryo-EM) is a technique that allows the structural characterization of macromolecules without the need for crystallization. For certain type of samples that are ideally suited for cryo-EM studies it has been possible to reach high-resolution structures following relatively standard procedures. Other biological systems remain highly challenging, even for cryo-EM. Challenges may involve the scarcity of the sample, poor stability of the complexes, and most often, the intrinsic flexibility of biological molecules. Among these challenging samples are large eukaryotic transcription complexes, which suffer from all such shortcomings. Here we report how we have recently tried to overcome those challenges in order to improve our structural understanding of the human transcription pre-initiation complex assembly and the transcription initiation process. Parallel efforts have also been carried out for budding yeast transcription initiation complexes, allowing comparisons that establish both the overall conservation and the specific structural differences between the two systems.

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“…These data suggest that XDP-related sequence variants may somehow alter expression of TAF1 , but the mechanisms underlying such alterations, as well as their downstream functional consequences, remain unclear. TAF1 encodes TATA-Binding Protein (TBP)-Associated Factor-1 (TAF1), the largest component of the multi-subunit TFIID complex which is involved in transcription initiation by RNA polymerase II (Poll II) (Anandapadamanaban et al, 2013; Grunberg and Hahn, 2013; Malkowska et al, 2013; Papai et al, 2011; Thomas and Chiang, 2006). Given the importance of TFIID dynamics for transcription in general, it is possible that perturbations in TAF1 could potentially have broad effects on gene expression, but to date there has been little information about transcriptional patterns in XDP cells.…”

Section: Introductionmentioning

confidence: 99%

X-linked Dystonia-Parkinsonism patient cells exhibit altered signaling via nuclear factor-kappa B

Vaine

Shin

Liu

et al. 2017

Neurobiology of Disease

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X-linked Dystonia-Parkinsonism (XDP) is a progressive neurodegenerative disease involving the loss of medium spiny neurons within the striatum. An XDP-specific haplotype has been identified, consisting of seven sequence variants which cluster around the human TAF1 gene, but a direct relationship between any of these variants and disease pathogenesis has not yet been demonstrated. Because the pathogenic gene lesion remains unclear, it has been difficult to predict cellular pathways which are affected in XDP cells. To address that issue, we assayed expression of defined gene sets in XDP vs. control fibroblasts to identify networks of functionally-related transcripts which may be dysregulated in XDP patient cells. That analysis derived a 51-gene signature distinguishing XDP vs. control fibroblasts which mapped strongly to nuclear factor-kappa B (NFκB), a transcription factor pathway also implicated in the pathogenesis of other neurodegenerative diseases, including Parkinson’s (PD) and Huntington’s disease (HD). Constitutive and TNFα-evoked NFκB signaling was further evaluated in XDP vs. control fibroblasts based on luciferase reporter activity, DNA binding of NFκB subunits, and endogenous target gene transcription. Compared to control cells, XDP fibroblasts exhibited decreased basal NFκB activity and decreased levels of the active NFκB p50 subunit, but increased target gene expression in response to TNFα. NFκB signaling was further examined in neural stem cells differentiated from XDP and control induced pluripotent stem cell (iPSC) lines, revealing a similar pattern of increased TNFα responses in the patient lines compared to controls. These data indicate that an NFκB signaling phenotype is present in both patient fibroblasts and neural stem cells, suggesting this pathway as a site of dysfunction in XDP.

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Structural bioinformatics of the general transcription factor TFIID

Cited by 25 publications

References 111 publications

Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

Frequent MYC coamplification and DNA hypomethylation of multiple genes on 8q in 8p11-p12-amplified breast carcinomas

Cryo-EM in the study of challenging systems: the human transcription pre-initiation complex

X-linked Dystonia-Parkinsonism patient cells exhibit altered signaling via nuclear factor-kappa B

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