Functional interrelationships between nuclear structure and transcriptional control: Contributions to regulation of cell cycle-and tissue-specific gene expression

Stein, Gary S.; Lian, Jane B.; Wijnen, André J. van; Montecino, Martín

doi:10.1002/(sici)1097-4644(199608)62:2<198::aid-jcb8>3.0.co;2-n

Cited by 33 publications

(8 citation statements)

References 90 publications

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“…Association of genes and cognate factors with the nuclear matrix may support the formation and/or activities of nuclear domains that facilitate transcriptional control (Guo et al, 1995;Merriman et al, 1995;Nickerson et al, 1995;Berezney et al, 1996;Chen et al, 1996;Nardozza et al, 1996;Stein et al, 1996;Alvarez et al, 1997;Davie, 1997;Grande et al, 1997;Jackson, 1997;Lindenmuth et al, 1997). Results from our laboratory indicate that the association of Runx transcription factors with the nuclear matrix is obligatory for activity (Zeng et al, 1998;Choi et al, 2001).…”

Section: Properties Of Transcriptionally Active Subnuclear Compartmentssupporting

confidence: 86%

Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression

et al. 2004

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We present an overview of Runx involvement in regulatory mechanisms that are requisite for fidelity of bone cell growth and differentiation, as well as for skeletal homeostasis and the structural and functional integrity of skeletal tissue. Runx-mediated control is addressed from the perspective of support for biological parameters of skeletal gene expression. We review recent findings that are consistent with an active role for Runx proteins as scaffolds for integration, organization and combinatorial assembly of nucleic acids and regulatory factors within the three-dimensional context of nuclear architecture.

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Section: Properties Of Transcriptionally Active Subnuclear Compartmentssupporting

confidence: 86%

Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression

et al. 2004

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“…These include drastic changes in nuclear morphology often seen in differentiation and in transformation to malignancy. The filamentous ribonucleoprotein network known as the nuclear matrix is a major component of nuclear structure (1)(2)(3)(4)(5). It serves to localize gene sequences and may maintain the distribution of regulatory factors throughout the nuclear space (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19).…”

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confidence: 58%

“…We compared the immunofluorescence pattern of AML-1B to that of SC-35, a spliceosome assembly factor that is associated with domains enriched in splicing factor (2,18,30). The results show that immunofluorescence signals for SC-35 and HA͞ AML-1B antibodies do not overlap (Fig.…”

Section: Resultsmentioning

confidence: 99%

Intranuclear targeting of AML/CBFα regulatory factors to nuclear matrix-associated transcriptional domains

Zeng

McNeil

Pockwinse

et al. 1998

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

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The AML͞CBF␣ runt transcription factors are key regulators of hematopoietic and bone tissue-specific gene expression. These factors contain a 31-amino acid nuclear matrix targeting signal that supports association with the nuclear matrix. We determined that the AML͞CBF␣ factors must bind to the nuclear matrix to exert control of transcription. Fusing the nuclear matrix targeting signal to the GAL4 DNA binding domain transactivates a genomically integrated GAL4 responsive reporter gene. These data suggest that AML͞CBF␣ must associate with the nuclear matrix to effect transcription. We used f luorescence labeling of epitopetagged AML-1B (CBFA2) to show it colocalizes with a subset of hyperphosphorylated RNA polymerase II molecules concentrated in foci and linked to the nuclear matrix. This association of AML-1B with RNA polymerase II requires active transcription and a functional DNA binding domain. The nuclear matrix domains that contain AML-1B are distinct from SC35 RNA processing domains. Our results suggest two of the requirements for AML-dependent transcription initiation by RNA polymerase II are association of AML-1B with the nuclear matrix together with specific binding of AML to gene promoters.Many observations suggest a linkage between nuclear architecture and the regulation of gene expression. These include drastic changes in nuclear morphology often seen in differentiation and in transformation to malignancy. The filamentous ribonucleoprotein network known as the nuclear matrix is a major component of nuclear structure (1-5). It serves to localize gene sequences and may maintain the distribution of regulatory factors throughout the nuclear space (6-19).The AML͞CBF␣ transcription factors are key regulators of hematopoietic and bone-tissue-specific gene expression (20)(21)(22)(23). We have recently shown that the transcriptionally active AML factors contain a specific sequence that targets them to the nuclear matrix (24). In contrast, several inactive forms of AML that lack this targeting signal do not associate with the matrix (24). The targeting sequence resides in a 31-aa segment (nuclear matrix targeting signal, NMTS; aa 351-381) within the C-terminal domain. This NMTS is physically distinct from the nuclear localization signal and functions autonomously to direct AML-1B (CBFA2) to the nuclear matrix (24). These findings suggest that association with nuclear structure may be an important aspect of the mechanisms of gene regulation.In this report we begin to examine the significance of the AML-1B transcription factor binding to the nuclear matrix. We show that AML-1B localizes to sites where there is also active transcription. We demonstrate that the NMTS, which directs AML-1B to the nuclear matrix, functions as a transactivation domain when interacting with an appropriate promoter. Furthermore, we show that the AML-1B transcription factor is targeted to discrete sites on the nuclear matrix. These sites also contain the hyperphosphorylated active form of RNA polymerase II. Colocalization of AML...

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“…60). Alterations in chromatin structure of both plant and animal genes have long been known to correlate with changes in gene expression (13,(61)(62)(63)(64)(65).…”

Section: Discussionmentioning

confidence: 99%

Hepatocyte Nuclear Factor 3 Relieves Chromatin-mediated Repression of the α-Fetoprotein Gene

Crowe¹,

Sang²,

Li³

et al. 1999

Journal of Biological Chemistry

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The ␣-fetoprotein gene (AFP) is tightly regulated at the tissue-specific level, with expression confined to endoderm-derived cells. We have reconstituted AFP transcription on chromatin-assembled DNA templates in vitro. Our studies show that chromatin assembly is essential for hepatic-specific expression of the AFP gene. While nucleosome-free AFP DNA is robustly transcribed in vitro by both cervical (HeLa) and hepatocellular (HepG2) carcinoma extracts, the general transcription factors and transactivators present in HeLa extract cannot relieve chromatin-mediated repression of AFP. In contrast, preincubation with either HepG2 extract or HeLa extract supplemented with recombinant hepatocyte nuclear factor 3 ␣ (HNF3␣), a hepatic-enriched factor expressed very early during liver development, is sufficient to confer transcriptional activation on a chromatin-repressed AFP template. Transient transfection studies illustrate that HNF3␣ can activate AFP expression in a non-liver cellular environment, confirming a pivotal role for HNF3␣ in establishing hepatic-specific gene expression. Restriction enzyme accessibility assays reveal that HNF3␣ promotes the assembly of an open chromatin structure at the AFP promoter. Combined, these functional and structural data suggest that chromatin assembly establishes a barrier to block inappropriate expression of AFP in non-hepatic tissues and that tissue-specific factors, such as HNF3␣, are required to alleviate the chromatin-mediated repression.

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Functional interrelationships between nuclear structure and transcriptional control: Contributions to regulation of cell cycle-and tissue-specific gene expression

Cited by 33 publications

References 90 publications

Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression

Runx2 control of organization, assembly and activity of the regulatory machinery for skeletal gene expression

Intranuclear targeting of AML/CBFα regulatory factors to nuclear matrix-associated transcriptional domains

Hepatocyte Nuclear Factor 3 Relieves Chromatin-mediated Repression of the α-Fetoprotein Gene

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