Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

Szemes, Marianna; György, Andrea; Paweletz, Cloud P.; Dobi, Albert; Ägoston, Dénes V.

doi:10.1007/s11064-005-9012-8

Cited by 82 publications

(114 citation statements)

References 57 publications

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“…However, we have found that SATB1 is identical to the 100-kDa AT-rich dsDNA-binding protein (tentatively named as dAT2). SATB1 (and also its related protein SATB2) are also expressed in development-and cell-specific fashion in the rat brain and are involved in regulating gene expression in differentiating neurons (33). 5 Many AT-binding proteins have a specific domain, called the AT-hook, thought to be critical to bind to AT-rich dsDNA sequences (51).…”

Section: Discussionmentioning

confidence: 99%

“…Following pentobarbital anesthesia, rat embryos were obtained from timed pregnancies; the brains were removed, and striatal and cortical primary embryonic neuronal cultures were prepared and maintained as published previously (29). C6 cells were obtained from the ATCC and cultured as described previously (33). For DNA molecular decoy assays, primary neuronal cultures were cotransfected with a DNA mixture containing the following: 0.5 g of the reporter plasmid 2700/ 703ENK-Luc, 2 g of competitor dsDNA corresponding to the rAT ENK region, or a control dsDNA (rAT ENK mut ) as described for EMSA above and 0.1 g of pCMV-Renilla luciferase.…”

Section: Methodsmentioning

confidence: 99%

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AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression

Dobi

Szemes

Lee

et al. 2006

Journal of Biological Chemistry

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During our search for transcriptional regulators that control the developmentally regulated expression of the enkephalin (ENK) gene, we identified AUF1. ENK, a peptide neurotransmitter, displays precise cell-specific expression in the adult brain. AUF1 (also known as heterogeneous nuclear ribonucleoprotein D) has been known to regulate gene expression through altering the stability of AU-rich mRNAs. We show here that in the developing brain AUF1 proteins are expressed in a spatiotemporally defined manner, and p37 and p40/42 isoforms bind to an AT-rich double-stranded (ds) DNA element of the rat ENK (rENK) gene. This AT-rich dsDNA sequence acts as a cis-regulatory DNA element and is involved in regulating the cell-specific expression of the ENK gene in primary neuronal cultures. The AT-rich dsDNA elements are present at ϳ2.5 kb 5 upstream of the rat, human, and mouse ENK genes. AUF1 proteins are shown here to provide direct interaction between these upstream AT-rich DNA sequences and the TATA region of the rENK gene. Double immunohistochemistry demonstrated that in the developing brain AUF1 proteins are expressed by proliferating neural progenitors and by differentiating neurons populating brain regions, which will not express the ENK gene in the adult, suggesting a repressor role for AUF1 proteins during enkephalinergic differentiation. Their subnuclear distribution and interactions with AT-rich DNA suggest that in the developing brain they can be involved in complex nuclear regulatory mechanisms controlling the development-and cell-specific expression of the ENK gene.The expression of the ENK 3 gene in the adult brain is highly cell-specific and spatially restricted. Many enkephalinergic neurons (i.e. express the ENK gene and use enkephalin peptides as neurotransmitters) are in the striatum (caudate putamen), and most of the other brain structures, such as cerebral cortex, are devoid of enkephalinergic neurons (1). This contrasting distribution is the result of the developmental process.ENK is a single copy gene encoding for preproenkephalin polypeptide, which is proteolytically cleaved, yielding four copies of Met-enkephalin and one copy of Leu-enkephalin peptides, which are endogenous ligands of opiate receptors (2). Enkephalins in the basal forebrain mediate social behavior, aggression, and reward and are implicated in mediating euphoric properties of drugs.The identity of neurons is established during neurodevelopment when multipotent progenitors differentiate into their various neurotransmitter phenotypes (3). Enkephalinergic differentiation, the cell-specific expression of the ENK gene, i.e. in spiny projection neurons in the striatum, takes place between embryonic day 14 (E14) and postnatal day 2 (P2) in the rat (4). It is during this period when transcription factors that directly regulate the developmental expression of neurotransmitter genes, such as ENK, are specifically expressed. They bind to cis-regulatory DNA elements and regulate the expression of their target genes, such as ENK (5), by restrict...

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Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression

Dobi

Szemes

Lee

et al. 2006

Journal of Biological Chemistry

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“…Satb2 is expressed by a subset of neurons throughout the cortical layers, but its expression is most prominent in layers 2-4 [18,[48][49][50]. Targeting of the Satb2 locus with a lacZ gene revealed that Satb2 expressing neurons normally extend axons across the corpus callosum [49].…”

Section: Satb2 and The Determination Of Callosal Projection Neuron Idmentioning

confidence: 99%

The determination of projection neuron identity in the developing cerebral cortex

Leone

Srinivasan

Chen

et al. 2008

Current Opinion in Neurobiology

334

316

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Here we review the mechanisms that determine projection neuron identity during cortical development. Pyramidal neurons in the mammalian cerebral cortex can be classified into two major classes: corticocortical projection neurons, which are concentrated in the upper layers of the cortex, and subcortical projection neurons, which are found in the deep layers. Early progenitor cells in the ventricular zone produce deep layer neurons that express transcription factors including Sox5, Fezf2, and Ctip2, which play important roles in the specification of subcortically projecting axons. Upper layer neurons are produced from progenitors in the subventricular zone, and the expression of Satb2 in these differentiating neurons is required for the formation of axonal projections that connect the two cerebral hemispheres. The Fezf2/Ctip2 and Satb2 pathways appear to be mutually repressive, thus ensuring that individual neurons adopt either a subcortical or callosal projection neuron identity at early times during development. The molecular mechanisms by which Satb2 regulates gene expression involves long-term epigenetic changes in chromatin configuration, which may enable cell fate decisions to be maintained during development.

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“…2 The SATB2 protein is involved in chromatin remodeling and transcriptional regulation through its ability to bind AT-rich DNA sequences known as matrix attachment regions (MAR). 3,4 Depending on the locus, it can either repress or activate transcription of specific genes. 5 Chromosomal translocations disrupting SATB2 have been associated with cleft palate (CP) and learning difficulties (OMIM #119540).…”

Section: Introductionmentioning

confidence: 99%

Further delineation of the SATB2 phenotype

et al. 2013

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Isolation and Characterization of SATB2, a Novel AT-rich DNA Binding Protein Expressed in Development- and Cell-Specific Manner in the Rat Brain

Cited by 82 publications

References 57 publications

AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression

AUF1 Is Expressed in the Developing Brain, Binds to AT-rich Double-stranded DNA, and Regulates Enkephalin Gene Expression

The determination of projection neuron identity in the developing cerebral cortex

Further delineation of the SATB2 phenotype

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