Identification of a Novel Slow-Muscle-Fiber Enhancer Binding Protein, MusTRD1

O'Mahoney, John V.; Guven, Kim; Lin, Jenshan; Joya, Josephine E.; Robinson, Charles Alexander; Wade, Robert; Hardeman, Edna C.

doi:10.1128/mcb.20.14.5361-5361.2000

Cited by 7 publications

(10 citation statements)

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“…The transcription functions of hMusTRD1͞BEN have not yet been well characterized biochemically. hMusTRD1͞BEN was reported first as a muscle-specific activator of the troponin I gene (7,40). It also seems to function as an activator in yeast one-hybrid assays (10).…”

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confidence: 99%

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Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxβ

Tussié-Luna

Bayarsaihan

Seto

et al. 2002

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

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TFII-I family proteins are characterized structurally by the presence of multiple reiterated I-repeats, each containing a putative helix-loophelix domain. Functionally, they behave as multifunctional transcription factors that are activated by a variety of extracellular signals. In studying their subcellular localization, we noticed that these transcription factors frequently reside in subnuclear domains͞dots. Because nuclear dots are believed often to harbor components of histone deacetylase enzymes (HDACs), we investigated whether TFII-I family proteins colocalize and interact with HDACs. Here, we show that TFII-I and its related member hMusTRD1͞BEN physically and functionally interact with HDAC3. The TFII-I family proteins and HDAC3 also show nearly identical expression patterns in early mouse development. Consistent with our earlier observation that TFII-I family proteins also interact with PIASx␤, a member of the E3 ligase family involved in the small ubiquitin-like modifier (SUMO) pathway, we show further that PIASx␤ physically and functionally interacts with HDAC3 and relieves the transcriptional repression exerted by HDAC3 upon TFII-I-mediated gene activation. These results suggest a complex interplay between two posttranslational pathways-histone modification and SUMOylation-brokered in part by TFII-I family proteins. E xtracellular signals often are transduced to the nucleus to bring about either up-regulation or down-regulation of specific genes. However, because the nuclear DNA is packaged with histones in nucleosomal arrays, to initiate transcriptional activation of any given gene, the promoter DNA must be accessible by the gene-specific activators as well as the basal machinery. Conversely, an actively transcribing genetic locus or a specific gene can be '''switched off'' by rendering the DNA inaccessible. Hence, the regulation of gene expression may begin at the level of chromatin alteration by concerted actions of histonemodifying enzymes. A histone acetyl transferase (HAT) acts by acetylating the tails of histones, lowering their positive charge and decreasing its stability of interactions with the DNA, upon which DNA becomes accessible. A histone deacetylase (HDAC) can reverse such an effect by deacetylating the histones, preserving their basic nature and, thereby, impeding DNA accessibility (1-3). Several other histone-tail modifications also have been described, such as methylation, ubiquitination, and phosphorylation (2, 3). It has been proposed that certain combinations of these modifications in one or more tails act sequentially or concomitantly to form a ''histone code'' recognized by specific regulatory proteins that lead to downstream events (4). It is generally believed that these enzymes are brought to the vicinity of the DNA and targeted to specific promoter regions through interactions with transcription factors, which can exert their effect only when the DNA is accessible. Therefore, to better understand how these enzymes regulate gene expression, considerable efforts have been spe...

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confidence: 99%

“…TFII-I belongs to a family of proteins characterized by the presence of I-repeats (5)(6)(7)(8)(9)(10)(11)(12)40). TFII-I is a ubiquitously expressed multifunctional transcription factor that is activated in response to various extracellular signals ranging from antigenic stimulation in B cells to growth factor signaling in fibroblasts.…”

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confidence: 99%

Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxβ

Tussié-Luna

Bayarsaihan

Seto

et al. 2002

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

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“…GTF2IRD1 (GTF2I repeat domain containing protein I) was initially identified in three independent yeast onehybrid screens as a protein that interacted with DNA baits composed of triplicated versions of the upstream regions of TNNI1 (O'Mahoney et al 1998), Hoxc8 (Bayarsaihan and Ruddle 2000), and goosecoid (Ring et al 2002). In the human, the gene encoding GTF2IRD1 is located in a cluster within chromosome 7q11.23 with two closely related genes; GTF2I encoding TFII-I and GTF2IRD2 encoding GTF2IRD2.…”

Section: Introductionmentioning

confidence: 99%

The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation

et al. 2015

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GTF2IRD1 is one of the three members of the GTF2I gene family, clustered on chromosome 7 within a 1.8 Mb region that is prone to duplications and deletions in humans. Hemizygous deletions cause Williams-Beuren syndrome (WBS) and duplications cause WBS duplication syndrome. These copy number variations disturb a variety of developmental systems and neurological functions. Human mapping data and analyses of knockout mice show that GTF2IRD1 and GTF2I underpin the craniofacial abnormalities, mental retardation, visuospatial deficits and hypersociability of WBS. However, the cellular role of the GTF2IRD1 protein is poorly understood due to its very low abundance and a paucity of reagents. Here, for the first time, we show that endogenous GTF2IRD1 has a punctate pattern in the nuclei of cultured human cell lines and neurons. To probe the functional relationships of GTF2IRD1 in an unbiased manner, yeast two-hybrid libraries were screened, isolating 38 novel interaction partners, which were validated in mammalian cell lines. These relationships illustrate GTF2IRD1 function, as the isolated partners are mostly involved in chromatin modification and transcriptional regulation, whilst others indicate an unexpected role in connection with the primary cilium. Mapping of the sites of protein interaction also indicates key features regarding the evolution of the GTF2IRD1 protein. These data provide a visual and molecular basis for GTF2IRD1 nuclear function that will lead to an understanding of its role in brain, behaviour and human disease.

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“…Each of the four principal fiber types expresses a distinct myosin heavy chain gene that largely determines fast or slow contractile speed [6] and many other muscle protein gene families contain members that are differentially expressed in fast and slow fibers [2, 5]. Recent studies have begun to characterize the cis-regulatory elements and trans-acting factors that direct fiber-type-specific gene expression [7,8,9]. …”

Section: Introductionmentioning

confidence: 99%

Human cytomegalovirus IE1 promoter/enhancer drives variable gene expression in all fiber types in transgenic mouse skeletal muscle

Hallauer

Hastings

2000

BMC Genet

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Background: Versatile transgenic manipulation of skeletal muscle requires knowledge of the expression profiles of diverse promoter/enhancer elements in the transcriptionally specialized fiber types of which muscle is composed. "Universal" viral promoters/enhancers, e.g., cytomegalovirus IE1 (CMV IE1), are of interest as reagents that may drive broad expression. However, a previous study noted a marked heterogeneity of CMV IE1-driven transgene expression among muscle fibers, raising the possibility of fiber-type-restricted expression. The purpose of the present study was to characterize CMV IE1-driven expression in terms of fiber type. Results:We produced two lines of transgenic mice carrying the CMV IE1/ β-galactosidase construct CMVLacZ, and analyzed transgene expression and fiber type by histochemical analysis of hindlimb muscle sections. In both lines CMVLacZ was expressed in all four major fiber types: type I (slow) and types IIA, IIB and IIX (fast). There was no unique pattern of fiber-type-preferential expression; fiber-type quantitative differences were observed but details varied between muscle regions and between lines. Both lines showed similar fiber-type-independent regional differences in overall expression levels, and a high level of within-fiber-type variability of expression, even among nearby fibers. The soleus muscle showed strong expression and comparatively little within-fibertype or between-fiber-type variability. Conclusions:The CMV IE1 promoter/enhancer is not fiber-type-restricted and can be useful for driving germ-line transgene expression in all four fiber types. However, not all fibers express the gene at high levels due in part to regional differences in overall expression levels, and to a high level of within-fiber-type variability. Given the multinucleate syncitial nature of muscle fibers, it is not likely that this variability is due to variegating heterochromatinization. The soleus muscle would make a suitable subject for near-uniform experimental gene expression driven by CMV IE1 elements.

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Identification of a Novel Slow-Muscle-Fiber Enhancer Binding Protein, MusTRD1

Cited by 7 publications

References 0 publications

Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxβ

Physical and functional interactions of histone deacetylase 3 with TFII-I family proteins and PIASxβ

The nuclear localization pattern and interaction partners of GTF2IRD1 demonstrate a role in chromatin regulation

Human cytomegalovirus IE1 promoter/enhancer drives variable gene expression in all fiber types in transgenic mouse skeletal muscle

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