Methylation-dependent SUMOylation of the architectural transcription factor HMGA2.

High mobility group A2 (HMGA2) is a chromatin-associated protein involved in the regulation of stem cell function, embryogenesis and cancer development. Although the protein does not contain a consensus SUMOylation site, it is shown to be SUMOylated. In this study, we demonstrate that the first lysine residue in the reported KKAE SUMOylation motif in HMGA2 can be methylated in vitro and in vivo by the Set7/9 methyltransferase.

Reexpression of LSAMP inhibits tumor growth in a preclinical osteosarcoma model.

Background: Osteosarcomas are the most common primary malignant tumors of bone, showing complex chromosomal rearrangements with multiple gains and losses. A frequent deletion within the chromosomal region 3q13.31 has been identified by us and others, and is mainly reported to be present in osteosarcomas.

Identification of target genes for wild type and truncated HMGA2 in mesenchymal stem-like cells.

Background: The HMGA2 gene, coding for an architectural transcription factor involved in mesenchymal embryogenesis, is frequently deranged by translocation and/or amplification in mesenchymal tumours, generally leading to over-expression of shortened transcripts and a truncated protein.

Methods: To identify pathways that are affected by sarcoma-associated variants of HMGA2, we have over-expressed wild type and truncated HMGA2 protein in an immortalized mesenchymal stem-like cell (MSC) line, and investigated the localisation of these proteins and their effects on differentiation and gene expression patterns.

Results: Over-expression of both transgenes blocked adipogenic differentiation of these cells, and microarray analysis revealed clear changes in gene expression patterns, more pronounced for the truncated protein.

Drosophila dSet2 functions in H3-K36 methylation and is required for development.

Lysine methylation has important functions in biological processes that range from heterochromatin formation to transcription regulation. Here, we demonstrate that Drosophila dSet2 encodes a developmentally essential histone H3 lysine 36 (K36) methyltransferase. Larvae subjected to RNA interference-mediated (RNAi) suppression of dSet2 lack dSet2 expression and H3-K36 methylation, indicating that dSet2 is the sole enzyme responsible for this modification in Drosophila melanogaster.

The Drosophila SET domain encoding gene dEset is essential for proper development.

We have identified dEset, the fly homolog of human SETDB1 and mouse ESET histone lysine methyltransferases (HKMTases) that methylates the lysine 9 residue of histone 3 (H3-K9) and negatively regulates transcription of target genes. By using spatio-temporal RNA interference we show that dEset is required at several stages of development coinciding with ecdysone pulses, possibly as a repressor of transcription of target genes. Several interacting partners, for example USP, spire, and cut up were identified in a yeast two-hybrid screen.

The acetyltransferase activity of Drosophila CBP is dispensable for regulation of the Dpp pathway in the early embryo.

The CBP protein is a transcriptional co-activator and histone acetyltransferase. Reduced expression of Drosophila CBP (dCBP) in the early embryo specifically impairs signaling by the TGF-beta molecules Dpp and Screw (Scw). This occurs by a failure to activate transcription of the tolloid (tld) gene, which codes for a protease that generates active Dpp and Scw ligands.

The Drosophila G9a gene encodes a multi-catalytic histone methyltransferase required for normal development.

Mammalian G9a is a histone H3 Lys-9 (H3-K9) methyltransferase localized in euchromatin and acts as a co-regulator for specific transcription factors. G9a is required for proper development in mammals as g9a-/g9a- mice show growth retardation and early lethality. Here we describe the cloning, the biochemical and genetical analyses of the Drosophila homolog dG9a.

The CBP coactivator functions both upstream and downstream of Dpp/Screw signaling in the early Drosophila embryo.

The CBP histone acetyltransferase plays important roles in development and disease by acting as a transcriptional coregulator. A small reduction in the amount of Drosophila CBP (dCBP) leads to a specific loss of signaling by the TGF-beta molecules Dpp and Screw in the early embryo. We show that the expression of Screw itself, and that of two regulators of Dpp/Screw activity, Twisted-gastrulation and the Tolloid protease, is compromised in dCBP mutant embryos.