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TESTIS-EXPRESSED GENE 10; TEX10

TESTIS-EXPRESSED GENE 10; TEX10

HGNC Approved Gene Symbol: TEX10Cytogenetic location: 9q31.1 Genomic coordinates (GRCh38): 9:100,302,083-100,352,941 (from NCBI)▼ DescriptionTEX10 is a subun...

HGNC Approved Gene Symbol: TEX10

Cytogenetic location: 9q31.1 Genomic coordinates (GRCh38): 9:100,302,083-100,352,941 (from NCBI)

▼ Description

TEX10 is a subunit of an SENP3 (612844)-associated complex that includes PELP1 (609455) and WDR18 and is involved in the maturation and nucleolar release of the large ribosomal subunit (Finkbeiner et al., 2011). TEX10 also plays a critical role in embryonic stem cell (ESC) self-renewal and pluripotency, early embryonic development, and somatic cell reprogramming via epigenetic regulation of super-enhancer activity (Ding et al., 2015).

▼ Cloning and Expression

Ding et al. (2015) noted that the TEX10 protein contains an Armadillo-type fold, an Armadillo-like helical structure, and a type 2 HEAT domain, which can be the interface for protein, DNA, and RNA binding.

Using biochemical fractionation of cell extracts, Finkbeiner et al. (2011) found that TEX10, as well as PELP1 and WDR18, is localized to mainly in the nucleoplasm with a subfraction concentrated in the nucleolus.

Immunofluorescence studies demonstrated that Tex10 is a nuclear protein highly expressed in mouse ESCs, although mRNA expression levels are also enriched in several adult mouse tissues such as testis, uterus, and lung (Ding et al., 2015).

▼ Mapping

Gross (2015) mapped the TEX10 gene to chromosome 9q31.1 based on an alignment of the TEX10 sequence (GenBank BC030652) with the genomic sequence (GRCh38).

▼ Gene Function

Using coimmunoprecipitation and mass spectrometry experiments in HeLa and HEK293T cells, Finkbeiner et al. (2011) showed that TEX10 formed a complex with PELP1 and WDR18 and that this complex was physically associated with SENP3. In siRNA knockdown experiments of PELP, TEX10, and WDR18, and an associated protein, MDN1 (618200), Finkbeiner et al. (2011) observed a reduction in the ratio of the mature 28S rRNA to the 32S precursor to 60%, 75%, 50%, and 30%, respectively, when compared with control cells, suggesting a role for the complex in ribosome biogenesis and the maturation of rRNA species. Depletion of these proteins in HeLa cells also resulted in the enlargement of the nucleoli due to accumulation of the large ribosomal subunit L27 (RPL27; 607526) exclusively within this organelle, suggesting that the complex has a role in the maturation and nucleolar release of the large ribosomal subunit.

Using affinity purification in mouse ESCs and interactome analysis, Ding et al. (2015) identified Tex10 as a novel binding partner of the pluripotency factor Sox2 (184429). Antibody-based immunoprecipitation assays confirmed this endogenous interaction. RNA-seq analyses of Tex10 knockdown cells demonstrated downregulation of 1,869 genes and upregulation of 2,109 genes that are highly enriched in ESCs, suggesting that Tex10 is involved with the pluripotency transcription network for stem cell maintenance. Single-cell transcription analysis of early mouse embryos showed that Tex10 is expressed in early embryonic development. Mouse Tex10 colocalized with Sox2 in mouse blastocysts. Knockdown of Tex10 in mouse zygotes by siRNA resulted in reduced embryo development from morula to blastocyst stage, suggesting that Tex10 is a key pluripotency factor that is required for early mouse development. In loss-of-function experiments, downregulation of Tex10 by shRNAs resulted in reduced ESC colony size and differentiated populations, suggesting that Tex10 is required for self-renewal and pluripotency. Tex10 is also required for efficient somatic cell reprogramming, as depletion of Tex10 dramatically reduced conventional Yamanaka reprogramming of mouse embryonic fibroblasts. In contrast, ectopic expression of Tex10 enhanced reprogramming, showing that Tex10 plays a critical role in the maintenance and establishment of pluripotency. In human ESCs, TEX10 was also shown to be crucial for stem cell maintenance, as depletion of TEX10 resulted in decreased programming efficiency. Using ChIP-seq to identify genomic targets of Tex10, Ding et al. (2015) found that Tex10 peaks were enriched at transcription start sites, and that Tex10 targets corresponded to Sox2 targets. Tex10 peaks were also enriched in regions of ESC super-enhancers, indicating that Tex10 positively regulates gene expression for ESCs. In Tex10 depletion assays, Ding et al. (2015) observed a reduction of enrichment of H3K27 acetylation modifications in the super-enhancer regions of Oct4 (164177), Nanog (607937), and Esrrb (602167), suggesting that Tex10 regulates super-enhancer activity through modulating histone acetylation. Tex10 was also shown to cooperate with p300 (602700) and Tet1 (607790) to control histone acetylation and DNA hypomethylation.

▼ Animal Model

Ding et al. (2015) showed that knockout of Tex10 in mice is embryonic lethal, likely prior to 7.5 dpc.

Tags: 9q31.1