Genomic Cloning and Characterization of the Mouse POZ/Zinc-Finger Protein ZF5

Yokoro, Kenjiro; Yanagidani, Akifumi; Obata, Takuya; Yamamoto, Shoso; Numoto, Michitaka

doi:10.1006/bbrc.1998.8675

Cited by 12 publications

(12 citation statements)

References 24 publications

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“…Four motif-based features were selected with a negative weight, implying that the presence of these features in a DNA sequence reduces the likelihood of them acting as a heart enhancer. For three of them, IRF, FREAC2, and ZF5, TFs believed to recognize these motifs have been reported to act as repressors or are not implicated in heart development (Yokoro et al 1998;Aitola et al 2000;Sherry 2002), supporting the notion that their negative weights are indicative of their absence from gene regulation in the heart. It is important to note that the classifier learns motifs or sequence patterns that are either over-or underrepresented in the heart enhancer set.…”

Section: Selected Features Have Been Previously Implicated In Heart Dmentioning

confidence: 79%

Genome-wide discovery of human heart enhancers

Narlikar¹,

Sakabe²,

Blanski³

et al. 2010

Genome Res.

112

135

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The various organogenic programs deployed during embryonic development rely on the precise expression of a multitude of genes in time and space. Identifying the cis-regulatory elements responsible for this tightly orchestrated regulation of gene expression is an essential step in understanding the genetic pathways involved in development. We describe a strategy to systematically identify tissue-specific cis-regulatory elements that share combinations of sequence motifs. Using heart development as an experimental framework, we employed a combination of Gibbs sampling and linear regression to build a classifier that identifies heart enhancers based on the presence and/or absence of various sequence features, including known and putative transcription factor (TF) binding specificities. In distinguishing heart enhancers from a large pool of random noncoding sequences, the performance of our classifier is vastly superior to four commonly used methods, with an accuracy reaching 92% in cross-validation. Furthermore, most of the binding specificities learned by our method resemble the specificities of TFs widely recognized as key players in heart development and differentiation, such as SRF, MEF2, ETS1, SMAD, and GATA. Using our classifier as a predictor, a genome-wide scan identified over 40,000 novel human heart enhancers. Although the classifier used no gene expression information, these novel enhancers are strongly associated with genes expressed in the heart. Finally, in vivo tests of our predictions in mouse and zebrafish achieved a validation rate of 62%, significantly higher than what is expected by chance. These results support the existence of underlying cis-regulatory codes dictating tissue-specific transcription in mammalian genomes and validate our enhancer classifier strategy as a method to uncover these regulatory codes.

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Section: Selected Features Have Been Previously Implicated In Heart Dmentioning

confidence: 79%

Genome-wide discovery of human heart enhancers

Narlikar¹,

Sakabe²,

Blanski³

et al. 2010

Genome Res.

112

135

View full text Add to dashboard Cite

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“…A number of mammalian BTB/ POZ-zinc finger factors are expressed in the central nervous system (52)(53)(54)(55)(56)(57), but the functional significance of this expression is not clear. In addition, the BTB/POZ domain factors BCL-6/LAZ3 and PLZF have been implicated in human malignancies involving chromosomal translocations (15,58,59).…”

Section: Discussionmentioning

confidence: 99%

Characterization of Two Novel Nuclear BTB/POZ Domain Zinc Finger Isoforms

Mitchelmore¹,

Kjærulff²,

Pedersen³

et al. 2002

Journal of Biological Chemistry

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BTB/POZ (broad complex tramtrack bric-a-brac/poxvirus and zinc finger) zinc finger factors are a class of nuclear DNA-binding proteins involved in development, chromatin remodeling, and cancer. However, BTB/POZ domain zinc finger factors linked to development of the mammalian cerebral cortex, cerebellum, and macroglia have not been described previously. We report here the isolation and characterization of two novel nuclear BTB/POZ domain zinc finger isoforms, designated HOF L and HOF S , that are specifically expressed in early hippocampal neurons, cerebellar granule cells, and gliogenic progenitors as well as in differentiated glia. During embryonic development of the murine cerebral cortex, HOF expression is restricted to the hippocampal subdivision. Expression coincides with early differentiation of presumptive CA1 and CA3 pyramidal neurons and dentate gyrus granule cells, with a sharp decline in expression at the CA1/subicular border. By using bromodeoxyuridine labeling and immunohistochemistry, we show that HOF expression coincides with immature non-dividing cells and is down-regulated in differentiated cells, suggesting a role for HOF in hippocampal neurogenesis. Consistent with the postulated role of the POZ domain as a site for protein-protein interactions, both HOF isoforms are able to dimerize. The HOF zinc fingers bind specifically to the binding site for the related promyelocytic leukemia zinc finger protein as well as to a newly identified DNA sequence.

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“…Apparently, regional specificity of quantitative hDAT expression is finely controlled. Recent in vitro studies have shown that hDAT expression in DA cell lines is activated by common TFs including NurrI, ZFP161 and Sp [7–11]. However, cis- acting elements such as Intron 1 [12, 13] for controlling hDAT activity represent a rarely explored subject.…”

Section: Introductionmentioning

confidence: 99%

Identification of an intronic cis-acting element in the human dopamine transporter gene

et al. 2011

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The human dopamine transporter gene (hDAT) encodes the dopamine transporter in dopamine (DA) neurons to regulate DA transmission. hDAT expression varies significantly from neuron to neuron, and from individual to individual so that dysregulation of hDAT is related to many neuropsychiatric disorders. It is critical to identify hDAT-specific cis-acting elements that regulate the hDAT expression. Previous studies showed that hDAT Intron 1 displayed inhibitory activity for reporter gene expression. Here we report that the hDAT Intron 1 contains a 121-bp fragment that down-regulated both SV40 and hDAT promoter activities by 80% in vitro. Subfragments of 121-bp still down-regulated the SV40 promoter but not the hDAT promoter, as supported by nuclear protein-binding activities. Collectively, 121-bp is a silencer in vitro that might coordinate with transcriptional activities both inside and outside 121-bp in regulation of hDAT.

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Genomic Cloning and Characterization of the Mouse POZ/Zinc-Finger Protein ZF5

Cited by 12 publications

References 24 publications

Genome-wide discovery of human heart enhancers

Genome-wide discovery of human heart enhancers

Characterization of Two Novel Nuclear BTB/POZ Domain Zinc Finger Isoforms

Identification of an intronic cis-acting element in the human dopamine transporter gene

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