Structure-specific DNA-binding proteins as the foundation for three-dimensional chromatin organization

Podgornaya, O. I.; Voronin, A.P.; Enukashvily, N. I.; Matveev, I. V.; Lobov, Ivan B.

doi:10.1016/s0074-7696(05)24006-8

Cited by 31 publications

(20 citation statements)

References 292 publications

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“…As expected, we found several known ubiquitous AT-binding proteins ( Table 2). These include DNA topoisomerase II A and B [30], poly(ADP-ribose) polymerase I [31,32], hnRNP U (SAF-A) [33,34] and hnRNPK [35]. These proteins are known to be either part of the nuclear matrix or frequently associated with it indicating that rAT ENK binds to the nuclear matrix.…”

Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

et al. 2006

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AT-rich DNA elements play an important role in regulating cell-specific gene expression. One of the AT-rich DNA binding proteins, SATB1 is a novel type of transcription factor that regulates gene expression in the hematopoietic lineage through chromatin modification. Using DNA-affinity purification followed by mass spectrometry we identified and isolated a related protein, SATB2 from the developing rat cerebral cortex. SATB2 shows homology to SATB1 and the rat protein is practically identical to the mouse and human SATB2. Using competitive EMSA, we show that recombinant SATB2 protein binds with high affinity and specificity to AT-rich dsDNA. Using RT-PCR, Western analysis and immunohistochemistry we demonstrate that SATB2 expression is restricted to a subset of postmitotic, differentiating neurons in the rat neocortex at ages E16 and P4. We suggest that similar to its homologue SATB1, SATB2 is also involved in regulating gene expression through altering chromatin structure in differentiating cortical neurons.

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Section: Resultsmentioning

confidence: 99%

Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

et al. 2006

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“…The question of a relationship between matrix attachment and heterochromatin has been widely discussed (for a review, see ref. 48). It is generally believed that S͞MARs may stop the expansion of heterochromatin and protect neighbor genes that are being transcribed from heterochromatinization.…”

Section: Discussion Drastic Changes In Chromatin Loop Domain Organizamentioning

confidence: 99%

Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts

Petrov

Pirozhkova

Carnac

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

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Fascioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder linked to partial deletion of integral numbers of a 3.3 kb polymorphic repeat, D4Z4, within the subtelomeric region of chromosome 4q. Although the relationship between deletions of D4Z4 and FSHD is well established, how this triggers the disease remains unclear. We have mapped the DNA loop domain containing the D4Z4 repeat cluster in human primary myoblasts and in murine-human hybrids. A nuclear matrix attachment site was found located in the vicinity of the repeat. Prominent in normal human myoblasts and nonmuscular human cells, this site is much weaker in muscle cells derived from FSHD patients, suggesting that the D4Z4 repeat array and upstream genes reside in two loops in nonmuscular cells and normal human myoblasts but in only one loop in FSHD myoblasts. We propose a model whereby the nuclear scaffold͞matrix attached region regulates chromatin accessibility and expression of genes implicated in the genesis of FSHD. The disorder is related to a short repeat array that remains after deletion of an integral number of tandemly arrayed 3.3-kb repeat units on chromosome 4. The size of this polymorphic locus (D4Z4) varies in normal individuals from 35 to 300 kb, whereas in FSHD patients it is consistently shorter than 35 kb (3). Partial deletion of the D4Z4 array on chromosome 4 ultimately leads to FSHD and is currently used as a diagnostic tool in genetic counseling to predict the probability of the disease (1,(3)(4)(5). A correlation exists between the extent of the deletion and its clinical expression: Indeed, patients with one to three repeats develop an early FSHD, whereas individuals with nine to 10 repeats exhibit a weaker form of the disease (5).Extensive efforts to identify gene transcripts associated with the 4q35-specific D4Z4 repeat, as potential FSHD candidate genes, have been largely unsuccessful (6). The 3.3-kb D4Z4 elements contain a cryptic DUX4 gene potentially coding for a double homeodomain protein (7), and an overall perturbation of mRNA expression profiles can be observed in FSHD patients (8-10), but the disease appears to result from an as yet unexplained mechanism with a genetic alteration not residing within a causative gene for the disease.The 4q35 genomic region ( Fig. 1) displays heterochromatic features and might exert repressive effects on neighboring genes with a mechanism similar to position effect variegation. A decreased D4Z4 repeat number consistently results in inappropriate up-regulation of adjacent FRG2, FRG1, and Ant1 in FSHD muscle (11-13). It has also been shown that a transcriptional repressor complex binds D4Z4, whose deletion would trigger overexpression by lack of repression (11). Indeed, overexpression of FRG1 in transgenic mice provokes a phenotype similar to that of FSHD (14). However, such a model of position effect has been recently challenged in two reports of an apparent lack of up-regulation of any 4q35 gene and because of the histone H4 acetylation state in FSHD lymph...

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“…The eukaryotic nucleus is a membrane-enclosed compartment supported by a complex scaffold or matrix of non-histone proteins (Podgornaya et al, 2003). Some nuclear scaffold proteins leave the nucleus at the time of nuclear envelope breakdown and are targeted to various mitotic apparati (Nickerson et al, 1992;Compton et al, 1992), whereas others, such as lamins, are dispersed throughout the cytoplasm (Jost et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

The nuclear scaffold protein SAF-A is required for kinetochore–microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles

Matsunaga

Morimoto

et al. 2011

Journal of Cell Science

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SummarySegregation of chromosomes during cell division requires correct formation of mitotic spindles. Here, we show that a scaffold attachment factor A (SAF-A), also known as heterogeneous nuclear ribonucleoprotein-U, contributes to the attachment of spindle microtubules (MTs) to kinetochores and spindle organization. During mitosis, SAF-A was localized at the spindles, spindle midzone and cytoplasmic bridge. Depletion of SAF-A by RNA interference induced mitotic delay and defects in chromosome alignment and spindle assembly. We found that SAF-A specifically co-immunoprecipitated with the chromosome peripheral protein nucleolin and the spindle regulators Aurora-A and TPX2, indicating that SAF-A is associated with nucleolin and the Aurora-A-TPX2 complex. SAF-A was colocalized with TPX2 and Aurora-A in spindle poles and MTs. Elimination of TPX2 or Aurora-A from cells abolished the association of SAF-A with the mitotic spindle. Interestingly, SAF-A can bind to MTs and contributes to the targeting of Aurora-A to mitotic spindle MTs. Our finding indicates that SAF-A is a novel spindle regulator that plays an essential role in kinetochore-MT attachment and mitotic spindle organization.

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Structure-specific DNA-binding proteins as the foundation for three-dimensional chromatin organization

Cited by 31 publications

References 292 publications

Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

Chromatin loop domain organization within the 4q35 locus in facioscapulohumeral dystrophy patients versus normal human myoblasts

The nuclear scaffold protein SAF-A is required for kinetochore–microtubule attachment and contributes to the targeting of Aurora-A to mitotic spindles

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