The Centromeric/Nucleolar Chromatin Protein ZFP-37 May Function to Specify Neuronal Nuclear Domains

Payen, Emmanuel; Verkerk, T.; Michalovich, David; Dreyer, Sandra D.; Winterpacht, Andreas; Lee, Brendan; Zeeuw, Chris I. De; Grosveld, Frank; Galjart, Niels

doi:10.1074/jbc.273.15.9099

Cited by 32 publications

(26 citation statements)

References 68 publications

(83 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…JHDM1A and JHDM1B directly bind to rDNA promoter and repress the transcription of rRNA genes through epigenetic mechanisms (37,38). Moreover, some zinc finger proteins such as ZFP37, ZNF274, and JAZ are located and function in the nucleolus (39)(40)(41). For instance, JAZ binds to RNA sequence and induces cell-cycle arrest and apoptosis through the p53 pathway (41).…”

Section: Discussionmentioning

confidence: 99%

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

Cheng

Liang

Geng

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

Epigenetic disruption of tumor suppressor genes is frequently involved in tumorigenesis. We identified a novel 19q13 KRAB domain-containing zinc finger protein, ZNF545/ZFP82, broadly expressed in normal tissues but downregulated in multiple tumor cell lines. The ZNF545 promoter contains a CpG island, which is frequently methylated in cell lines. The transcriptional silencing of ZNF545 could be reversed by pharmacologic or genetic demethylation, indicating direct epigenetic silencing. ZNF545 was also frequently methylated in multiple primary tumors of nasopharyngeal, esophageal, lung, gastric, colon, and breast, but rarely in normal epithelial tissues and paired normal tissues. ZNF545 is located in the nucleus and mainly sequestered in nucleoli, functioning as a repressor. ZNF545 is able to repress NF-kB and AP-1 signaling pathways, whereas ectopic expression of ZNF545 in silenced tumor cells significantly inhibited their growth and induced apoptosis. Functional studies showed that ZNF545 was involved in ribosome biogenesis through inhibiting the activity of rDNA promoter and decreasing cellular protein translation efficiency. Thus, we identified ZNF545 as a novel tumor suppressor inducing tumor cell apoptosis, repressing ribosome biogenesis and target gene transcription. The tumor-specific methylation of ZNF545 could be an epigenetic biomarker for cancer diagnosis. Mol Cancer Res; 10(7); 925-36. Ó2012 AACR.

show abstract

Section: Discussionmentioning

confidence: 99%

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

Cheng

Liang

Geng

et al. 2012

Molecular Cancer Research

View full text Add to dashboard Cite

show abstract

“…Previous studies have shown that Kid-1 is connected to heterochromatin through its adaptor protein KRIP-1 (12)(13)(14)57). The connection between the nucleolus and heterochromatin has also been made for Modulo, a modifier of position-effect variegation in Drosophila (58), and for Zfp37, a murine Cys 2 His 2 -zinc finger protein with a truncated KRAB-A domain that is expressed in neuronal cells (59). In the case of Modulo, it has been hypothesized that the nucleolus balances the amount of Modulo available for heterochromatin formation and position-effect variegation (58).…”

Section: Discussionmentioning

confidence: 99%

Expression of the Transcriptional Repressor Protein Kid-1 Leads to the Disintegration of the Nucleolus

Huang

Philippin

O’Leary

et al. 1999

Journal of Biological Chemistry

View full text Add to dashboard Cite

The rat Kid-1 gene codes for a 66-kDa protein with KRAB domains at the NH 2 terminus and two Cys 2 His 2 -zinc finger clusters of four and nine zinc fingers at the COOH terminus. It was the first KRAB-zinc finger protein for which a transcriptional repressor activity was demonstrated. Subsequently, the KRAB-A domain was identified as a widespread transcriptional repressor motif. We now present a biochemical and functional analysis of the Kid-1 protein in transfected cells. The full-length Kid-1 protein is targeted to the nucleolus and adheres tightly to as yet undefined nucleolar structures, leading eventually to the disintegration of the nucleolus. The tight adherence and nucleolar distribution can be attributed to the larger zinc finger cluster, whereas the KRAB-A domain is responsible for the nucleolar fragmentation. Upon disintegration of the nucleolus, the nucleolar transcription factor upstream binding factor disappears from the nucleolar fragments. In the absence of Kid-1, the KRIP-1 protein, which represents the natural interacting partner of zinc finger proteins with a KRAB-A domain, is homogeneously distributed in the nucleus, whereas coexpression of Kid-1 leads to a shift of KRIP-1 into the nucleolus. Nucleolar run-ons demonstrate that rDNA transcription is shut off in the nucleolar fragments. Our data demonstrate the functional diversity of the KRAB and zinc finger domains of Kid-1 and provide new functional insights into the regulation of the nucleolar structure.

show abstract

“…Centromeric heterochromatin displays a perinucleolar localization in human cells, especially in neuronal cells (Manuelidis, 1984;O'Keefe et al, 1992;Leger et al, 1994;Payen et al, 1998). A fraction of rRNA genes, which are silenced in nucleoli of all cell types regardless of their metabolic activity, is organized as dense heterochromatin-like structures.…”

Section: Nucleolar Tau Interacts With At-rich Pericentromeric Satellimentioning

confidence: 99%

Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization

Sjöberg

Shestakova

Mansuroglu

et al. 2006

Journal of Cell Science

140

143

View full text Add to dashboard Cite

The microtubule-associated tau protein participates in the organization and integrity of the neuronal cytoskeleton. A nuclear form of tau has been described in neuronal and non-neuronal cells, which displays a nucleolar localization during interphase but is associated with nucleolar-organizing regions in mitotic cells. In the present study, based on immunofluorescence, immuno-FISH and confocal microscopy, we show that nuclear tau is mainly present at the internal periphery of nucleoli, partially colocalizing with the nucleolar protein nucleolin and human AT-rich α-satellite DNA sequences organized as constitutive heterochromatin. By using gel retardation, we demonstrate that tau not only colocalizes with, but also specifically binds to, AT-rich satellite DNA sequences apparently through the recognition of AT-rich DNA stretches. Here we propose a functional role for nuclear tau in relation to the nucleolar organization and/or heterochromatinization of a portion of RNA genes. Since nuclear tau has also been found in neurons from patients with Alzheimer's disease (AD), aberrant nuclear tau could affect the nucleolar organization during the course of AD. We discuss nucleolar tau associated with AT-rich α-satellite DNA sequences as a potential molecular link between trisomy 21 and AD.

show abstract

The Centromeric/Nucleolar Chromatin Protein ZFP-37 May Function to Specify Neuronal Nuclear Domains

Cited by 32 publications

References 68 publications

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

A Novel 19q13 Nucleolar Zinc Finger Protein Suppresses Tumor Cell Growth through Inhibiting Ribosome Biogenesis and Inducing Apoptosis but Is Frequently Silenced in Multiple Carcinomas

Expression of the Transcriptional Repressor Protein Kid-1 Leads to the Disintegration of the Nucleolus

Tau protein binds to pericentromeric DNA: a putative role for nuclear tau in nucleolar organization

Contact Info

Product

Resources

About