Novel repressor of the human <i>FMR1</i> gene − identification of p56 human (GCC)<sub>n</sub>‐binding protein as a Krüppel‐like transcription factor ZF5

Orlov, Sergey; Kuteykin-Teplyakov, Konstantin; Ignatovich, I. A.; Dizhe, Ella B.; Mirgorodskaya, O. A.; Grishin, A. V.; Guzhova, Olga B.; Prokhortchouk, Egor; Guliy, Pavel V.; Perevozchikov, A. P.

doi:10.1111/j.1742-4658.2007.06006.x

Cited by 24 publications

(16 citation statements)

References 40 publications

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“…Tcf3, which is best known for its involvement in Wnt signaling [45], is associated with the GO category ‘segmentation’, consistent with a recently described role in restricting induction of the anterior-posterior axis [46]. Zfp161 (ZF5), a repressor of the human fragile X-mental retardation 1 (FMR1) gene [47], is associated with gene expression clusters primarily in the embryo (Supplementary Figure S4). …”

Section: Resultssupporting

confidence: 56%

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

et al. 2010

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Sequence-specific binding by transcription factors (TFs) interprets regulatory information encoded in the genome. Using recently published universal protein binding microarray (PBM) data on the in vitro DNA binding preferences of these proteins for all possible 8-base-pair sequences, we examined the evolutionary conservation and enrichment within putative regulatory regions of the binding sequences of a diverse library of 104 nonredundant mouse TFs spanning 22 different DNA-binding domain structural classes. We found that not only high affinity binding sites, but also numerous moderate and low affinity binding sites, are under negative selection in the mouse genome. These 8-mers occur preferentially in putative regulatory regions of the mouse genome, including CpG islands and non-exonic ultraconserved elements (UCEs). Of TFs whose PBM ‘bound’ 8-mers are enriched within sets of tissue-specific UCEs, many are expressed in the same tissue(s) as the UCE-driven gene expression. Phylogenetically conserved motif occurrences of various TFs were also enriched in the noncoding sequence surrounding numerous gene sets corresponding to Gene Ontology categories and tissue-specific gene expression clusters, suggesting involvement in transcriptional regulation of those genes. Altogether, our results indicate that many of the sequences bound by these proteins in vitro, including lower affinity DNA sequences, are likely to be functionally important in vivo. This study not only provides an initial analysis of the potential regulatory associations of 104 mouse TFs, but also presents an approach for the functional analysis of TFs from any other metazoan genome as their DNA binding preferences are determined by PBMs or other technologies.

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Section: Resultssupporting

confidence: 56%

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

et al. 2010

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“…Since CGC motifs within Box D and its downstream flanking sequence both were important for complex formation, antibodies against the cellular transcription factor Zfp64 also were used in EMSAs. This protein is a member of the Kruppelassociated box (KRAB) family and is a zinc finger protein with a consensus binding motif of CGCG (46). As with the E2F transcription factor family, no supershifts or disruption of complexes was observed (data not shown).…”

Section: Resultsmentioning

confidence: 95%

A Sequence within the Varicella-Zoster Virus (VZV) OriS Is a Negative Regulator of DNA Replication and Is Bound by a Protein Complex Containing the VZV ORF29 Protein

Khalil

Arvin

Jones

et al. 2011

J Virol

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Varicella-zoster virus (VZV), human herpesvirus 3, is a member of the Alphaherpesvirinae and is the etiologic agent of two distinct clinical syndromes in humans: chicken pox (varicella), occurring during primary infection, and shingles (zoster), occurring after reactivation from latency (12). The VZV genome is a 125-kb linear double-stranded DNA molecule and is predicted to code for at least 71 proteins. The viral DNA is made up of long and short unique segments designated U L and U S , respectively, both of which are bounded by inverted and terminal repeat sequences IR s /TR s (14). The VZV genome contains two copies of an origin of DNA replication (OriS), flanked by ORF62 and ORF63 genes, within the IR s /TR s repeats bounding the U S segment (13,14,57,58). VZV has been shown to encode homologues of all seven viral gene products required for herpes simplex virus type 1 (HSV-1) DNA replication. These include the viral DNA polymerase and its associated processivity factor, a heterotrimeric helicase/primase complex, a single-strand DNA-binding protein (SSB), and a site-specific origin-binding protein (OPB) (20). However, while the two viruses have similar genomic organizations and encode similar DNA replication factors, the architecture of the VZV and HSV-1 OriS regions differs significantly (Fig. 1A).The two VZV OriS contain an AT-rich palindrome and three 10-bp consensus binding sites [5Ј-C(G/A)TTCGCACT-3Ј] for the VZV OBP encoded by VZV ORF51 (57, 59). These binding sites, designated Boxes A, B, and C, all are located upstream of the AT-rich palindrome. They are identical (Boxes A and B) or nearly identical (Box C) to the consensus binding site for the HSV-1 U L 9 OBP, with which the VZV ORF51 OBP shares 54.8% similarity and 46.5% identity (7,30,59). In addition to these cis elements, there is a characteristic GA-rich sequence immediately downstream of the AT-rich region in the VZV origin which is not present in the HSV-1 origin (14,19).All three OBP binding sites in the VZV origin are oriented in the same direction and are present on the same strand of the viral DNA. In contrast, in the HSV-1 OriS, binding sites for the UL9 OBP (Boxes I, II, and III) occur both upstream and downstream of the AT-rich region. Boxes I and II are located upstream and downstream on opposite strands of the DNA and are oriented in opposite directions. Box III is located upstream of Box I but is oriented in the same direction and occurs on the same DNA strand as Box II. Mutational analysis has shown that efficient HSV-1 origin-dependent DNA replication requires the presence of all three UL9 binding sites as well as the central AT-rich region (3,15,22,38,45,58,61).

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“…AP2-α, ZF5 and Pax-2, all function in the regulation of distinct transcriptional programs. ZF5 is a kruppel-type TF which has been shown to regulate the expression of the fragile-X causative gene FMR1 (46). In addition, binding sites for ZF5 are enriched in the genetic promoters of clock-regulated genes, as have binding sites for the known BRCA1 interacting TFs; E2F, AP-1 and NF-Y, SP1 and Oct-1 (14,15,47).…”

Section: Discussionmentioning

confidence: 99%

Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis

Gorski

Savage

Mulligan

et al. 2011

Nucleic Acids Research

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A role for BRCA1 in the direct and indirect regulation of transcription is well established. However, a comprehensive view of the degree to which BRCA1 impacts transcriptional regulation on a genome-wide level has not been defined. We performed genome-wide expression profiling and ChIP-chip analysis, comparison of which revealed that although BRCA1 depletion results in transcriptional changes in 1294 genes, only 44 of these are promoter bound by BRCA1. However, 27% of these transcripts were linked to transcriptional regulation possibly explaining the large number of indirect transcriptional changes observed by microarray analysis. We show that no specific consensus sequence exists for BRCA1 DNA binding but rather demonstrate the presence of a number of known and novel transcription factor (TF)- binding sites commonly found on BRCA1 bound promoters. Co-immunoprecipitations confirmed that BRCA1 interacts with a number of these TFs including AP2-α, PAX2 and ZF5. Finally, we show that BRCA1 is bound to a subset of promoters of genes that are not altered by BRCA1 loss, but are transcriptionally regulated in a BRCA1-dependent manner upon DNA damage. These data suggest a model, whereby BRCA1 is present on defined promoters as part of an inactive complex poised to respond to various genotoxic stimuli.

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Novel repressor of the human FMR1 gene − identification of p56 human (GCC)_n‐binding protein as a Krüppel‐like transcription factor ZF5

Cited by 24 publications

References 40 publications

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

A Sequence within the Varicella-Zoster Virus (VZV) OriS Is a Negative Regulator of DNA Replication and Is Bound by a Protein Complex Containing the VZV ORF29 Protein

Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis

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Novel repressor of the human FMR1 gene − identification of p56 human (GCC)n‐binding protein as a Krüppel‐like transcription factor ZF5

Cited by 24 publications

References 40 publications

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

Conservation and regulatory associations of a wide affinity range of mouse transcription factor binding sites

A Sequence within the Varicella-Zoster Virus (VZV) OriS Is a Negative Regulator of DNA Replication and Is Bound by a Protein Complex Containing the VZV ORF29 Protein

Profiling of the BRCA1 transcriptome through microarray and ChIP-chip analysis

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Novel repressor of the human FMR1 gene − identification of p56 human (GCC)_n‐binding protein as a Krüppel‐like transcription factor ZF5