Back to basics:Sox genes

Department of Neurobiology and Anatomy, University of Utah, Salt Lake City, Utah 84132, USA.
Developmental Dynamics (Impact Factor: 2.67). 08/2007; 236(8):2356-66. DOI: 10.1002/dvdy.21218
Source: PubMed

ABSTRACT Sox genes are indispensable for multiple aspects of development. This primer briefly describes shared properties of the Sox gene family, and five well-characterized examples of vertebrate developmental mechanisms governed by Sox gene subgroups: testis development, central nervous system neurogenesis, oligodendrocyte development, chondrogenesis, and neural crest cell development. Also featured is an interview about current issues in the field with experts Jonas Muhr, Ph.D. and Robert Kelsh, Ph.D.

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    ABSTRACT: The neural transcription factor SOX11 is present at specific stages during embryo development with a very restricted expression in adult tissue, indicating precise regulation of transcription. SOX11 is strongly up-regulated in some malignancies and have a functional role in tumorgenesis. With the aim to explore differences in epigenetic regulation of SOX11 expression in normal versus neoplastic cells, we investigated methylation and histone modifications related to the SOX11 promoter and the possibility to induce re-expression using histone deacetylase (HDAC) or EZH2 inhibitors. The epigenetic regulation of SOX11 was investigated in distinct non-malignant cell populations (n = 7) and neoplastic cell-lines (n = 42) of different cellular origins. DNA methylation was assessed using bisulfite sequencing, methylation-specific melting curve analysis, MethyLight and pyrosequencing. The presence of H3K27me3 was assessed using ChIP-qPCR. The HDAC inhibitors Vorinostat and trichostatin A were used to induce SOX11 in cell lines with no endogenous expression. The SOX11 promoter shows a low degree of methylation and strong enrichment of H3K27me3 in non-malignant differentiated cells, independent of cellular origin. Cancers of the B-cell lineage are strongly marked by de novo methylation at the SOX11 promoter in SOX11 non-expressing cells, while solid cancer entities display a more varying degree of SOX11 promoter methylation. The silencing mark H3K27me3 was generally present at the SOX11 promoter in non-expressing cells, and an increased enrichment was observed in cancer cells with a low degree of SOX11 methylation compared to cells with dense methylation. Finally, we demonstrate that the HDAC inhibitors (vorinostat and trichostatin A) induce SOX11 expression in cancer cells with low levels of SOX11 methylation. We show that SOX11 is strongly marked by repressive histone marks in non-malignant cells. In contrast, SOX11 regulation in neoplastic tissues is more complex involving both DNA methylation and histone modifications. The possibility to re-express SOX11 in non-methylated tissue is of clinical relevance, and was successfully achieved in cell lines with low levels of SOX11 methylation. In breast cancer patients, methylation of the SOX11 promoter was shown to correlate with estrogen receptor status, suggesting that SOX11 may be functionally re-expressed during treatment with HDAC inhibitors in specific patient subgroups.
    BMC Cancer 04/2015; 15(1):273. DOI:10.1186/s12885-015-1208-y · 3.32 Impact Factor
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    ABSTRACT: SOX2 is a stem cell transcription factor that plays a crucial role in the regulation of embryonic development. It is one of the genes in a set of factors (Oct4, SOX2, Nanog) that are able to reprogram human somatic cells to pluripotent stem cells. Overexpression of SOX2 has been described in all types of lung cancer tissues, including small cell and squamous cell carcinoma but also adenocarcinoma. An in-depth view of the spectrum of genomic alterations in small cell lung cancer (SCLC) has identified SOX2 as a potential target for therapeutic intervention. Amplification of 3q, the most common genomic aberration in squamous lung cancer, has been demonstrated in the evolution of preinvasive squamous lung cancer and implicates SOX2 as a key target of this dynamic process, making SOX2 and its downstream effector components potential targets for biological therapeutics of squamous carcinomas. SOX2 is expressed in nearly 20% of lung adenocarcinoma and is associated with poor prognosis. SOX2 activity was found to promote squamous identity instead of a loss of cellular differentiation consistent with the role of SOX2 as a "lineage-survival oncogene." Interestingly, SOX2 transcription factor is the predominant downstream target of EGFR signaling and plays a major role in self-renewal growth and expansion of side population cells. In light of the complex actions of SOX2 in regulating normal and tumor development, the elucidation of SOX2-dependent pathways may identify new therapeutic vulnerabilities in lung cancer and uncover additional common pathways between cancer, normal development, and the maintenance of pluripotency.
    06/2013; 2(3):172-9. DOI:10.3978/j.issn.2218-6751.2013.01.01
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    ABSTRACT: The high mobility group (HMG) family transcription factor Sox9 is critical for induction and maintenance of neural stem cell pool in the central nervous system (CNS). In the spinal cord and retina, Sox9 is also the master regulator that defines glial fate choice by mediating the neurogenic-to-gliogenic fate switch. On the other hand, the genetic repertoire governing the maintenance and fate decision of neural progenitor pool in the cerebellum has remained elusive. By employing the Cre/loxP strategy, we specifically inactivated Sox9 in the mouse cerebellum. Unexpectedly, the self-renewal capacity and multipotency of neural progenitors at the cerebellar ventricular zone (VZ) were not perturbed upon Sox9 ablation. Instead, the mutants exhibited an increased number of VZ-derived neurons including Purkinje cells and GABAergic interneurons. Simultaneously, we observed continuous neurogenesis from Sox9-null VZ at late gestation, when normally neurogenesis ceases to occur and gives way for gliogenesis. Surprisingly, glial cell specification was not affected upon Sox9 ablation. Our findings suggest Sox9 may mediate the neurogenic-to-gliogenic fate switch in mouse cerebellum by modulating the termination of neurogenesis, and therefore indicate a functional discrepancy of Sox9 between the development of cerebellum and other major neural tissues.
    Molecular Brain 04/2015; 8(1):25. DOI:10.1186/s13041-015-0115-0 · 4.35 Impact Factor