The Roles of HMGA Proteins

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Despite a wealth of biochemical in vitro data on the HMGA proteins of various organisms, their biological role in chromatin is still not convincingly clarified. Current evidence suggests that HMG proteins serve a global role in chromatin by conferring a more “open” configuration to chromatin regions that are more accessible to transcriptional regulators (Bianchi and Agresti, 2005; Catez et al., 2004). In addition, there is massive evidence that HMGA proteins act as architectural factors that facilitate assembly of functional transcription factor complexes (enhanceosomes) at DNA target sites by various mechanisms. Several studies analysing altered expression levels of HMGA genes in animals have demonstrated that the chromosomal HMGA proteins have important cellular roles. Knock-out of the mouse HMGA1 gene revealed that HMGA1 is required for normal sperm development (Liu et al., 2003), and that disrupting the HMGA1 gene results in a decreased expression of the insulin receptor, largely impairing insulin signalling (Foti et al., 2005). Inactivation of the HMGA2 gene causes the mouse pygmy phenotype, and a deficiency in fat tissue, probably due to affected fat-cell proliferation (Anand and Chada, 2000; Zhou et al., 1995). Moreover, mouse HMGA2 is target of a regulatory miRNA and is involved in stem cell aging (Hammond and Sharpless, 2008).

Plant HMGA proteins bind A/T-rich DNA and they display high affinity for four-way junction DNA (Nieto-Sotelo et al., 1994; Webster et al., 1997; Zhang et al., 2003). Moreover, they specifically interact with nucleosome particles and are released from chromatin by limited nuclease digestion, suggesting preferential binding to transcriptionally active chromatin (Arwood and Spiker, 1990; Lichota and ...

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...odology is established in the Grasser-lab (Launholt et al., 2006; Pedersen et al., 2010; Pedersen et al., 2011).

WP4. Another approach to learn about the function of HMGA is the identification of protein interactors. Therefore, recombinant HMGA fused to gluthatione S transferase (GST) is immobilised (in parallel GST alone serves as control) and is incubated with nuclear protein extracts. Proteins that specifically bind GST-HMGA (but not GST) are identified by MALDI-TOF mass spectrometry that is perfomed at the Biochemistry Department at Regensburg University. In parallel, the existing HMGA antibody (Launholt et al., 2006) is used for immunoprecipitation of HMGA from plant protein extracts. Specifically coprecipitating proteins are again identified by mass spectrometry. The identification of interacting proteins will help elucidating the role of HMGA in Arabidopsis.

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