Disease relevance of HmgD

• This difference shows that the enthalpy of dehydration of apolar groups at the HMG-D/DNA interface is not fully compensated by the energy of van der Waals interactions between these groups, i.e. the packing density at the interface must be lower than for the sequence-specific Sox-5 HMG box [1].
• During overexpression and purification of HMG-D from E. coli, a key DNA binding residue, methionine 13, undergoes oxidation to methionine sulfoxide [2].

High impact information on HmgD

• Finally, we show that HMG-D bends DNA and may confer a superhelical DNA conformation at a natural DNA binding site in the Drosophila fushi tarazu scaffold-associated region [3].
• HMG-D is an architecture-specific protein that preferentially binds to DNA containing the dinucleotide TG [3].
• HMG-D, the Drosophila melanogaster homologue of HMG 1 protein, is associated with early embryonic chromatin in the absence of histone H1 [4].
• HMG D is encoded by a single-copy gene that maps to 57F8-11 on the right arm of chromosome 2 [5].
• This protein, HMG D, shares most of the characteristics of vertebrate HMG proteins; it is extractable from nuclei with 0.35 M NaCl, is soluble in 5% perchloric acid, is relatively small (molecular weight of 12,000), has both a high basic (24%) and high acidic (24%) amino acid content, and is a DNA-binding protein [5].

Biological context of HmgD

• The titers of the HMG proteins HMGD, HMGZ, and D1 are highest in ovaries and at the beginning of embryonic development [6].
• Using site specific antibodies against helices I and III of HMGD and HMGZ and against the AT-hook motif of D1, protein-specific staining patterns have been observed during embryonic development [6].
• The genes for dHMG-D and dHMG-Z are located on adjacent loci in the genome and each contains two introns [7].
• To understand better the basis of this preference, we have studied the binding of HMG1 (which has two tandem HMG boxes linked by a basic extension to a long acidic tail) and Drosophila HMG-D (one HMG box linked by a basic region to a short and less acidic tail), and their HMG-box domains, to 88 bp and 75 bp DNA minicircles [8].
• The C-terminal tail of HMG-D confers high-affinity DNA binding, has an undefined structure, and appears to make direct contacts in the major groove of DNA via residues that are potentially regulated by phosphorylation [9].

Anatomical context of HmgD

• We have now studied the association of HMG-D with chromatin using a cell-free system for chromatin reconstitution derived from Drosophila embryos [10].
• However, we have observed an unusual sequestering of HMG D maternal mRNA within the periphery of oocytes during late oogenesis and zygotic expression confined to the developing embryonic nervous system [11].

Associations of HmgD with chemical compounds

• Conversely, deleting the methyl group from thymines promotes the interaction of the DNA with HMG-D but diminishes its interaction with c-Abl [12].
• In contrast, c-Abl and HMG-D respond very differently to deletion or addition of the 5-methyl group of pyrimidine bases in the major groove [12].
• Oxidation of a critical methionine modulates DNA binding of the Drosophila melanogaster high mobility group protein, HMG-D [2].

Physical interactions of HmgD

• HMG-D interacts with DNA during the early phases of nucleosome assembly but is gradually displaced as chromatin matures [10].

Enzymatic interactions of HmgD

• Electrospray ionization mass spectroscopic analyses revealed that Drosophila HMGD and Chironomus HMG1a and HMG1b are double-phosphorylated and that Drosophila HMGZ is triple-phosphorylated [13].

Other interactions of HmgD

• We also observe genetic interactions between the HmgD/Z deficiency and some, but not all, known Brahma targets [14].
• To investigate their function genetically we have generated a defined deficiency uncovering the functionally redundant genes encoding HMGD and HMGZ, the Drosophila counterparts of HMGB1-3 in mammals [14].
• Our results argue against a proposal of a shared role of HMGD and histone H1 in Drosophila chromatin [6].
• Furthermore, we present evidence that binding of a high-mobility-group protein, HMG-D, to the Dpp-responsive enhancer of tinman as well as to the Tinman protein may be involved in the formation of a fully active enhancer complex [15].

References