Mechanism and Role of SOX2 Repression in Seminoma: Relevance to Human Germline Specification

Ritu Kushwaha, Nirmala Jagadish, Manjunath Kustagi, Geetu Mendiratta, Marco Seandel, Rekha Soni, James E. Korkola, Venkata Thodima, Andrea Califano, George J. Bosl, R. S.K. Chaganti

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Human male germ cell tumors (GCTs) are derived from primordial germ cells (PGCs). The master pluripotency regulator and neuroectodermal lineage effector transcription factor SOX2 is repressed in PGCs and the seminoma (SEM) subset of GCTs. The mechanism of SOX2 repression and its significance to GC and GCT development currently are not understood. Here, we show that SOX2 repression in SEM-derived TCam-2 cells is mediated by the Polycomb repressive complex (PcG) and the repressive H3K27me3 chromatin mark that are enriched at its promoter. Furthermore, SOX2 repression in TCam-2 cells can be abrogated by recruitment of the constitutively expressed H3K27 demethylase UTX to the SOX2 promoter through retinoid signaling, leading to expression of neuronal and other lineage genes. SOX17 has been shown to initiate human PGC specification, with its target PRDM1 suppressing mesendodermal genes. Our results are consistent with a role for SOX2 repression in normal germline development by suppressing neuroectodermal genes.

Original languageEnglish (US)
Pages (from-to)772-783
Number of pages12
JournalStem Cell Reports
Volume6
Issue number5
DOIs
StatePublished - May 10 2016

ASJC Scopus subject areas

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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    Kushwaha, R., Jagadish, N., Kustagi, M., Mendiratta, G., Seandel, M., Soni, R., Korkola, J. E., Thodima, V., Califano, A., Bosl, G. J., & Chaganti, R. S. K. (2016). Mechanism and Role of SOX2 Repression in Seminoma: Relevance to Human Germline Specification. Stem Cell Reports, 6(5), 772-783. https://doi.org/10.1016/j.stemcr.2016.04.002