Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete for binding to mouse satellite DNA

Radic, Marko; Saghbini, Michael; Elton, Terry S.; Reeves, Raymond; Hamkalo, Barbara A.

doi:10.1007/bf00360537

Cited by 83 publications

(71 citation statements)

References 41 publications

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“…Likewise, HMGA1a-GFP proteins were associated with chromosomes during mitosis. This distribution corresponds to previous immunfluorescence studies (Amirand et al, 1998;Martelli et al, 1998) and earlier observations, describing that HMGA1a proteins bind preferentially to A-tracts within heterochromatic regions (Radic et al, 1992;Reeves and Elton, 1987;Strick and Laemmli, 1995;Zhao et al, 1993). Nevertheless, we found that HMGA1a-GFP fusion proteins associate dynamically with DNA/chromatin throughout the cell cycle.…”

Section: Discussionsupporting

confidence: 92%

Dynamic interaction of HMGA1a proteins with chromatin

Harrer

Lührs

Bustin

et al. 2004

Journal of Cell Science

101

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High-mobility-group proteins A1 (HMGA1; previously named HMGI/Y) function as architectural chromatin-binding proteins and are involved in the transcriptional regulation of several genes. We have used cells expressing proteins fused to green fluorescent protein (GFP) and fluorescence recovery after photobleaching (FRAP) to analyze the distribution and dynamics of HMGA1a in vivo. HMGA1-GFP proteins localize preferentially to heterochromatin and remain bound to chromosomes during mitosis. FRAP experiments showed that they are highly mobile components of euchromatin, heterochromatin and of mitotic chromosomes, although with different resident times. For a more-detailed investigation on the interaction of HMGA1a with chromatin, the contribution of the AT-hook DNA-binding motifs was analyzed using point-mutated HMGA1a-GFP proteins. Furthermore, by inhibiting kinase or histone deacetylase activities, and with the help of fusion proteins lacking specific phosphorylation sites, we analyzed the effect of reversible modifications of HMGA1a on chromatin binding. Collectively our data show that the kinetic properties of HMGA1a proteins are governed by the number of functional AT-hooks and are regulated by specific phosphorylation patterns. The higher residence time in heterochromatin and chromosomes, compared with euchromatic regions, correlates with an increased phosphorylation level of HMGA1a. The regulated dynamic properties of HMGA1a fusion proteins indicate that HMGA1 proteins are mechanistically involved in local and global changes in chromatin structure.

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Section: Discussionsupporting

confidence: 92%

Dynamic interaction of HMGA1a proteins with chromatin

Harrer

Lührs

Bustin

et al. 2004

Journal of Cell Science

101

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“…Moreover, we have found the presence of short repeats such as CTG(A/C)A(A/T), GA(C/T/G)AAAAC or (C/G)AAAA(C/G) that are very similar to other centromeric motifs described in other vertebrates [11]. These sequence motifs could be important elements in centromere structure and function [11,28,29].…”

Section: Resultsmentioning

confidence: 97%

A new EcoRI family of satellite DNA in lampreys

et al. 1996

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“…These localizations suggest that the HMGA proteins are actively involved in the dynamic changes in chromatin structure that occur during chromosome condensation in the cell division cycle. Indeed, treatment of cells with distamycin -a drug which displaces histone H1 and HMGA1 from SARs and other AT-rich sequences -causes marked decondensation of centromeric heterochromatin and substantial metaphase chromosome elongation, indicating that both histone H1 and HMGA1 are necessary for chromosome condensation (25,26). However, it is also in such metaphase chromosomes that both the histone H1 and HMGA1 proteins are maximally phoshorylated by the cell cycle-dependent cdc2 kinase (see below), and most loosely bound to the substrate DNA.…”

Section: Hmga Proteins and Chromosome Dynamicsmentioning

confidence: 99%

“…It has also been shown that the HMGA1 proteins bind to multiple sites in mouse satellite DNA. Studies using the AT-binding drugs Hoechst 33258 and distamycin A show that these drugs cause an incomplete condensation of centromeric chromatin by competing with the HMGA1 proteins for binding to satellite DNA (26).…”

Section: Hmga Proteins and Chromosome Dynamicsmentioning

confidence: 99%

The HMGA proteins: A myriad of functions (Review)

Cleynen

Ven²

2008

Int J Oncol

214

243

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Abstract. The 'high mobility group' HMGA protein family consists of four members: HMGA1a, HMGA1b and HMGA1c, which result from translation of alternative spliced forms of one gene and HMGA2, which is encoded for by another gene. HMGA proteins are characterized by three DNA-binding domains, called AT-hooks, and an acidic carboxy-terminal tail. HMGA proteins are architectural transcription factors that both positively and negatively regulate the transcription of a variety of genes. They do not display direct transcriptional activation capacity, but regulate gene expression by changing the DNA conformation by binding to AT-rich regions in the DNA and/or direct interaction with several transcription factors. In this way, they influence a diverse array of normal biological processes including cell growth, proliferation, differentiation and death. Both HMGA1 and HMGA2 are hardly detectable in normal adult tissue but are abundantly and ubiquitously expressed during embryonic development. In malignant epithelial tumors as well as in leukemia, however, expression of HMGA1 is again strongly elevated to embryonic levels thus leading to ectopic expression of (fetal) target genes. HMGA2 overexpression also has a causal role in inducing neoplasia. Besides overexpression of full length HMGA proteins in different tumors, the HMGA genes are often involved in chromosomal rearrangements. Such translocations are mostly detected in benign tumors of mesenchymal origin and are believed to be one of the most common chromosomal rearrangements in human neoplasia. To provide clarity in the abundance of articles on this topic, this review gives a general overview of the nuclear functions and regulation of the HMGA genes and corresponding proteins.

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Hoechst 33258, distamycin A, and high mobility group protein I (HMG-I) compete for binding to mouse satellite DNA

Cited by 83 publications

References 41 publications

Dynamic interaction of HMGA1a proteins with chromatin

Dynamic interaction of HMGA1a proteins with chromatin

A new EcoRI family of satellite DNA in lampreys

The HMGA proteins: A myriad of functions (Review)

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