A DNA-binding Element for a Steroid Receptor-binding Factor Is Flanked by Dual Nuclear Matrix DNA Attachment Sites in the c-myc Gene Promoter

Lauber, Andrea H.; Barrett, Thomas J.; Subramaniam, Malayannan; Schuchard, Mark D.; Spelsberg, Thomas C.

doi:10.1074/jbc.272.39.24657

Cited by 15 publications

(17 citation statements)

References 86 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7) is consistent with a direct interaction of MENT with such DNA. In particular, MENT may recognize specific DNA sequences such as the c-Myc scaffold-associated region, which contains a prominent A⅐T-rich DNA sequence (87). These elements may have a much stronger affinity for DNA-binding proteins in the context of a nucleosome array than as naked DNA as has been proposed for repeated A⅐T-rich sequences (88), thus accounting for the apparent absence of sequence-specific interactions of MENT with DNA in vitro.…”

Section: Discussionmentioning

confidence: 99%

MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member

Grigoryev

Bednář

Woodcock

1999

Journal of Biological Chemistry

108

102

View full text Add to dashboard Cite

Terminal cell differentiation is correlated with the extensive sequestering of previously active genes into compact transcriptionally inert heterochromatin. In vertebrate blood cells, these changes can be traced to the accumulation of a developmentally regulated heterochromatin protein, MENT. Cryoelectron microscopy of chicken granulocyte chromatin, which is highly enriched with MENT, reveals exceptionally compact polynucleosomes, which maintain a level of higher order folding above that imposed by linker histones. The amino acid sequence of MENT reveals a close structural relationship with serpins, a large family of proteins known for their ability to undergo dramatic conformational transitions. Conservation of the "hinge region" consensus in MENT indicates that this ability is retained by the protein. MENT is distinguished from the other serpins by being a basic protein, containing several positively charged surface clusters, which are likely to be involved in ionic interactions with DNA. One of the positively charged domains bears a significant similarity to the chromatin binding region of nuclear lamina proteins and with the A⅐T-rich DNA-binding motif, which may account for the targeting of MENT to peripheral heterochromatin. MENT ectopically expressed in a mammalian cell line is transported into nuclei and is associated with intranuclear foci of condensed chromatin.In eukaryotic cells, DNA in association with histones and other nuclear proteins forms a DNA-protein complex or chromatin that exhibits varying levels of compaction (1, 2). Chromatin is folded hierarchically, with the basic level represented by a repeated structural unit, the nucleosome, comprising 200 Ϯ 40-bp 1 DNA of which 146 bp make about 1.7 superhelical turns around the histone octamer (3), and the remainder (linker DNA) is not constrained by core histones. Linker DNA is usually associated with the ninth (linker) histone, which brings the core-proximal segments of linker DNA together (4 -6). In vitro, nucleosome arrays fold into ϳ30-nm-wide chromatin fibers having a characteristic zigzag organization at low ionic strength with separate nucleosomes connected by extended linkers (7-10). If the extent of DNA charge shielding or neutralization is increased (e.g. by increasing the salt concentration in the medium), the zigzag chromatin fibers first become more compact and then self-associate to form the next level of higher order folding, which involves closer contacts between nucleosomes (11-15). Modulation of chromatin folding constitutes a potentially important regulatory mechanism that may influence the locus-specific accessibility of DNA templates to the trans-acting factors mediating transcription (16 -19), replication (20), transposition (21), and perhaps other templatedependent functions.It has been known for many years that, in interphase nuclei, the chromatin is not uniformly decondensed but contains a considerable amount of more compact material, called heterochromatin (22), which generally increases during the terminal stages of euka...

show abstract

Section: Discussionmentioning

confidence: 99%

MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member

Grigoryev

Bednář

Woodcock

1999

Journal of Biological Chemistry

108

102

View full text Add to dashboard Cite

show abstract

“…The receptor-binding factor (RBF) for the avian oviduct progesterone receptor has also been demonstrated to bind to a 54-bp element in the 5 0 -flanking region of the progesteroneregulated avian c-myc gene and NM-like attachment sites flank the RBF element in the c-myc promoter [Lauber et al, 1997]. GRIP120, one of the co-factors that interacts with glucocorticoid receptors, has been shown to be identical to the heterogeneous nuclear ribonucleoprotein U (hnRNP U), a NM protein binding to RNA as well as to SARs [Eggert et al, 1997].…”

Section: Nucler Matrix (Nm)mentioning

confidence: 98%

Nuclear matrix proteins as biomarkers in prostate cancer

Leman

Getzenberg

2002

J of Cellular Biochemistry

View full text Add to dashboard Cite

The nuclear matrix (NM) is the structural framework of the nucleus that consists of the peripheral lamins and pore complexes, an internal ribonucleic protein network, and residual nucleoli. The NM contains proteins that contribute to the preservation of nuclear shape and its organization. These protein components better known as the NM proteins have been demonstrated to be tissue specific, and are altered in many cancers, including prostate cancer. Alterations in nuclear morphology are hallmarks of cancer and are believed to be associated with changes in NM protein composition. Prostate cancer is the most frequently diagnosed cancer in American men and many investigators have identified unique NM proteins that appear to be specific for this disease. These NM protein changes are associated with the development of prostate cancer, as well as in some cases being indicative of cancer stage. Identification of these NM proteins specific for prostate cancer provides an insight to understanding the molecular changes associated with this disease. This article reviews the role of NM proteins as tumor biomarkers in prostate cancer and the potential application of these proteins as therapeutic targets in the treatment of this disease.

show abstract

“…For example, MARs have been implicated in defining physical boundaries between genes (27,28). In addition, MARs often are found in close association with active elements such as enhancers (19,27,28), promoters (29,30), and putative replication origins (31,32), potentially serving to anchor these elements to specific nuclear matrix sites. MARs have also been described as regions susceptible to histone H1 displacement and, therefore, chromatin ''opening'' by way of the interaction of minor groove binding proteins like HMG-I͞Y (33).…”

mentioning

confidence: 99%

Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions

Sakai

Bottaro

Davidson

et al. 1999

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

View full text Add to dashboard Cite

The intronic Ig heavy chain (IgH) enhancer, which consists of the core enhancer f lanked by 5 and 3 matrix attachment regions, has been implicated in control of IgH locus recombination and transcription. To elucidate the regulatory functions of the core enhancer and its associated matrix attachment regions in the endogenous IgH locus, we have introduced targeted deletions of these elements, both individually and in combination, into an IgH a͞b -heterozygous embryonic stem cell line. These embryonic stem cells were used to generate chimeric mice by recombination activating gene-2 (Rag-2)-deficient blastocyst complementation, and the effects of the introduced mutations were assayed in mutant B cells. We find that the core enhancer is necessary and sufficient to promote normal variable (V), diversity (D), and joining (J) segment recombination in developing B lineage cells and IgH locus transcription in mature B cells. Surprisingly, the 5 and 3 matrix attachment regions were dispensable for these processes. Multiple enhancer elements have been identified within the IgH locus, including the intronic enhancer (E) between J H and C (3, 4) and a series of enhancers (collectively referred to as the 3Ј IgH regulatory region) that lie downstream of C␣ (reviewed in ref. 5). Extensive transfection and transgenic studies delineated the E sequences based on ability to direct lymphoid-specific expression (3, 4, 6-8; reviewed in refs. 9-11). Studies of cell lines with spontaneous E region deletions suggested this enhancer was necessary for IgH expression in precursor-B cells (12, 13), but dispensable for expression in terminally differentiated B cell lines (14-17).Transfection assays defined a small 220-bp core element (hereafter referred as cE) within E, which is necessary and sufficient for transcriptional stimulation; cE contains multiple binding sites for both ubiquitous and cell-specific factors with negative and positive activity (reviewed in ref. 18). Biochemical assays further identified two AT-rich nuclear matrix attachment regions (MARs) flanking cE (19). MARs are generally defined by the ability to bind to the nuclear matrix, which is a rather poorly defined protein fraction containing factors important for regulation of gene expression in addition to structural scaffold components (reviewed in refs. 20-25). Despite a strictly biochemical definition, several functions for MARs have been proposed (reviewed in refs. 20, 23-27). For example, MARs have been implicated in defining physical boundaries between genes (27, 28). In addition, MARs often are found in close association with active elements such as enhancers (19, 27, 28), promoters (29, 30), and putative replication origins (31, 32), potentially serving to anchor these elements to specific nuclear matrix sites. MARs have also been described as regions susceptible to histone H1 displacement and, therefore, chromatin ''opening'' by way of the interaction of minor groove binding proteins like HMG-I͞Y (33).The E-associated MARs initially were implicated as a...

show abstract

A DNA-binding Element for a Steroid Receptor-binding Factor Is Flanked by Dual Nuclear Matrix DNA Attachment Sites in the c-myc Gene Promoter

Cited by 15 publications

References 86 publications

MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member

MENT, a Heterochromatin Protein That Mediates Higher Order Chromatin Folding, Is a New Serpin Family Member

Nuclear matrix proteins as biomarkers in prostate cancer

Recombination and transcription of the endogenous Ig heavy chain locus is effected by the Ig heavy chain intronic enhancer core region in the absence of the matrix attachment regions

Contact Info

Product

Resources

About