Contributions of Nuclear Architecture to Transcriptional Control

Stein, Gary S.; Wijnen, A. J. Van; Lian, Jane B.; Montecino, Martín

doi:10.1016/s0074-7696(08)61233-4

Cited by 35 publications

(33 citation statements)

References 129 publications

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“…Posttranscriptional modi®cations of histones have been implicated in the physiological control of chromatin structure (Stein et al, 2000). Acetylation of the lysine-residue of nucleosomal histones is assumed to lead to local chromatin decondensation, resulting in increasing accessibility of particular DNA regions for RNA polymerase complexes.…”

Section: How Is Telomerase Regulated?mentioning

confidence: 99%

Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?

2002

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Telomerase activation is observed in almost 90% of human cancers but not in normal tissues of somatic origin and thus is a critical step for multistep carcinogenesis. A more thorough understanding of telomerase regulation may provide not only a molecular basis of cancer progression but also as a way to manipulate telomerase activity as a potential therapeutic modality. Recent progress in studies on telomerase regulation has shown that telomerase activation is achieved at various steps, including transcriptional and post-transcriptional levels of the telomerase reverse transcriptase (hTERT) gene. Although a number of potentially important mechanisms of telomerase activation have been proposed, none of the current models can fully explain tumor-speci®c activation of telomerase, suggesting a need for further extensive analysis. This review includes a summary of recent works on telomerase regulation and a discussion of how we can overcome this situation.

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Section: How Is Telomerase Regulated?mentioning

confidence: 99%

Complex regulatory mechanisms of telomerase activity in normal and cancer cells: How can we apply them for cancer therapy?

2002

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“…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][21][22][23][24][25]. Despite a strictly biochemical definition, several functions for MARs have been proposed (reviewed in refs.…”

mentioning

confidence: 99%

“…Despite a strictly biochemical definition, several functions for MARs have been proposed (reviewed in refs. 20,[23][24][25][26][27]. For example, MARs have been implicated in defining physical boundaries between genes (27,28).…”

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.

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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...

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“…Transcription is also in part regulated by the nuclear scaffold which regulates the association and organisation of genes and transcription factors. Certain observations implicate that active transcription complexes are bound to the nuclear lamina and transcription factors as well as active genes are reported to be enriched in nuclear matrix preparations (Jackson et al, 1985;Stein et al, 1995). The contribution of nuclear lamins in transcription has been suggested by different studies.…”

Section: Hutchinson-gilford Progeria Syndromementioning

confidence: 99%