Disease relevance of Hmgn1

• The UV hypersensitivity of Hmgn1(-/-) MEFs could be rescued by transfection with plasmids expressing wild-type HMGN1 protein, but not with plasmids expressing HMGN1 mutants that do not bind to nucleosomes or do not unfold chromatin [1].
• The human gene for HMG-14 has been localized to the Down syndrome region of Chromosome (Chr) 21 and may be involved in the etiology of this syndrome [2].
• In tumor tissues (Lewis lung carcinoma and lymphoma NQ35), the amount of HMG17/HMG14 is not greatly altered but HMGI levels rise considerably, reaching 10% in Lewis lung carcinoma [3].
• 3-Amino-benzamide, a specific inhibitor of (ADP-ribose)n synthetase, increased mouse mammary tumor virus RNA levels with an accompanying decrease in endogenous ADP-ribosylation of HMG 14 and 17 [4].

High impact information on Hmgn1

• In Hmgn1-/- cells, loss of HMGN1 elevates the steady-state levels of phospho-S10-H3 and enhances the rate of stress-induced phosphorylation of S10-H3 [5].
• Using antibodies against the phosphorylated residues, we show that H3 and HMG-14 phosphorylation is mediated via different MAP kinase (MAPK) cascades, depending on the stimulus [6].
• The nucleosomal response associated with immediate-early gene induction is mediated via alternative MAP kinase cascades: MSK1 as a potential histone H3/HMG-14 kinase [6].
• A mitogen- and anisomycin-stimulated kinase phosphorylates HMG-14 in its basic amino-terminal domain in vivo and on isolated mononucleosomes [7].
• Nobotanin B caused concentration-dependent inhibition of glucocorticoid-induced de-poly(ADP-ribosyl)ation of HMG 14 and 17 and histone H1 in intact 34I cells [8].

Biological context of Hmgn1

• Re-expression of wild-type HMGN1, but not of the mutant HMGN1 protein that does not bind to chromatin, in Hmgn1-/- MEFs, decreased the levels of N-cadherin and restored the Hmgn1+/+ phenotype [9].
• This paper summarizes recent advances from studies of Hmgn1 knockout mice and genetically engineered cell lines that are beginning to reveal the diverse roles that HMGN proteins play in DNA repair and transcription within mammalian cells [10].
• During myogenesis the level of both HMG-14 and HMG-17 mRNA decreased to less than 20% of that found in myoblasts [11].
• These results identify HMG-14 and HMG-17 as constitutive components of mouse oocyte and embryonic chromatin and establish a link between the structure of embryonic chromatin and the normal progression of embryonic development [12].
• When puff formation began, the chromosome site assumed a very intense fluorescence, which disappeared again when the Balbiani ring was recondensed. - Protein extracts of salivary gland nuclei were found on immunoblots to contain one major protein fraction that reacted with the anti-HMG 14 antibody [13].

Anatomical context of Hmgn1

• The corneal epithelium of Hmgn1(-/-) mice is thin, has a reduced number of cells, is poorly stratified, is depleted of suprabasal wing cells, and its most superficial cell layer blisters [14].
• Immunofluorescence analysis reveals a complete co-localization of HMGN1 and p 63 in small clusters of basal corneal epithelial cells of wild-type mice, and an absence of p 63 expressing cells in the central region of the Hmgn1(-/-) cornea [14].
• DNA microarray analysis of Hmgn1+/+ and Hmgn1-/- embryonic fibroblasts identified N-cadherin as a potential HMGN1 gene target [9].
• The expression of chromosomal proteins HMG-14 and HMG-17 during cellular differentiation was studied in cultured mouse myoblasts [11].
• An antibody was raised against "high mobility group" nuclear protein 14 (HMG 14) from calf thymus, known to be associated with actively transcribed chromatin [13].

Associations of Hmgn1 with chemical compounds

• The nucleosomal response refers to the rapid phosphorylation of histone H3 on serine 10 and HMG-14 on serine 6 that occurs concomitantly with immediate-early (IE) gene induction in response to a wide variety of stimuli [6].
• Two of these, HMG-14 and HMG-17(identified by solubility in trichloroacetic acid, electrophoretic mobility on SDS-polyacrylamide gels and by amino acid composition) will partially inhibit the endogenous mouse cell histone deacetylase enzymes when added to in vitro assay mixtures [15].
• Exhaustive extraction of mouse tissues with perchloric acid has been used together with reverse-phase HPLC and electrophoresis to quantify the amounts of chromosomal proteins HMG17, HMG14 and HMGI, relative to histone H1 [3].
• The identity and purity of these HMG-14 and -17 protein species were assayed by polyacrylamide gel electrophoresis and amino acid analysis [16].
• MNNG treatment of cells caused a rapid and transient increase in ADP ribosylation of histone H1 and HMG 1 and 2, whereas (ADP-ribose)n on HMG 14 and 17 was not affected [17].

Other interactions of Hmgn1

• Localization of nuclear proteins related to high mobility group protein 14 (HMG 14) in polytene chromosomes [13].
• Nevertheless, all these agents elicit phosphorylation of ribosomal and pre-ribosomal S6, histone H3 and HMG-14, and the induction of c-fos and c-jun, showing that neither cascade is absolutely essential for these responses [18].
• The LLC-TNF and LLC-IL6 tissues of mice treated with TZT-1027 had in common the independent alteration of the non-histone chromosomal protein HMG-14 and transcription factor 1 for heat shock gene [19].
• Of these 150 genes, all but two, HMG14 and carboxypeptidase E, were upregulated with age [20].

Analytical, diagnostic and therapeutic context of Hmgn1

• Indirect immunofluorescence with anti-HMG 14 antibody in polytene nuclei was restricted to the active puffs [13].
• Amino acid analysis and peptide mapping of all four proteins demonstrated that HMG I and Y were not phosphorylated modifications of HMG 14 or 17 [21].

References