title: HMG20A is required for SNAI1-mediated epithelial to mesenchymal transition.
abstract: HMG20A is a high mobility group (HMG) domain containing protein homologous to HMG20B, a core subunit of the Lys-specific demethylase 1/REST co-repressor 1 (LSD1-CoREST) histone demethylase complex. Here, we show that HMG20A can replace HMG20B and, therefore, they are mutually exclusive subunits of the complex. Both proteins interact through a coiled-coil domain with BHC80, another subunit of the LSD1-CoREST complex. To investigate the functional differences between the two proteins, we performed transcriptomic analysis of HMG20A- and HMG20B-depleted cells. Analysis of the misregulated genes in HMG20A-knockdown cells evidenced a high proportion of genes related to the epithelial-to-mesenchymal transition (EMT) process. EMT occurs during embryonic development or during the course of malignant cancer progression and consists in the dynamic and reversible transitions between epithelial and mesenchymal phenotypes. We show that HMG20A together with LSD1 are required for SNAI1-dependent repression of epithelial genes and for (transforming growth factor β) TGF-β-triggered EMT. Importantly, HMG20A-depleted cells displayed reduced binding of LSD1 to epithelial gene promoters and increased methylation of lysine 4 of histone H3, suggesting a role of HMG20A in recruiting or in stabilizing the complex at the chromatin. SNAI1 and the TGF-β-related transcription factor SMAD4 were found to be associated with the LSD1-CoREST complex containing HMG20A. Furthermore, we show that HMG20A-depleted cells displayed reduced motility and invasion activity. Finally, we show that expression of HMG20A correlates positively with mesenchymal markers and negatively with epithelial markers in human tumor samples. Taken together, our data demonstrate that HMG20A is essential for the mesenchymal phenotype.
authors: Molecular Biology Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors: S
authors: S
authors: Rivero
authors: Molecular Biology Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors: M
authors: M
authors: Ceballos-Chávez
authors: Cell Therapy and Regenerative Medicine Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Seville, Spain.
authors: S S
authors: SS
authors: Bhattacharya
authors: Molecular Biology Department, Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER), Consejo Superior de Investigaciones Científicas (CSIC), Seville, Spain.
authors: J C
authors: JC
authors: Reyes
mesh_terms: D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D063990:Gene Ontology; D057809:HEK293 Cells; D006609:High Mobility Group Proteins / Q000502:physiology*; D056466:Histone Demethylases / Q000378:metabolism; D006801:Humans; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000235:genetics / Q000378:metabolism; D051901:Smad4 Protein / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C408987:HMG20A protein, human; D006609:High Mobility Group Proteins; C497796:SMAD4 protein, human; C000604407:SNAI1 protein, human; D051901:Smad4 Protein; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D056466:Histone Demethylases; C495195:KDM1A protein, human
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