Functional gene cassettes in development.

Jan, Yuh Nung

doi:10.1073/pnas.90.18.8305

Cited by 53 publications

(27 citation statements)

References 38 publications

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“…12 out of 15 E-boxes are located upstream of the transcription initiation sites. This sequence, CANNTG, is recognized by the bHLH family of proteins (34), which includes regulators of nerve cell differentiation (8,23). Another family of proteins implicated in neural development recognizes the POU consensus sequence (35); five out of six POU motifs are clustered in a 250-bp region of intron I.…”

Section: Resultsmentioning

confidence: 99%

“…A fusion gene containing this promoter fragment and the bacterial lac z coding region mimicked the expression pattern of the endogenous RI␤ gene in the central nervous system of transgenic mice (20). Analysis of sequence and protein binding activity of this DNA (21) has identified a complex array of recognition sequences for general transcriptional activators like Sp1 (22), developmental regulators like bHLH and POUdomain proteins (6,23), and physiological regulators such as immediate-early gene products (9) and steriod hormone receptors (SHR) (24,25). To address the functional role of these various binding sites in vivo, we performed a deletion analysis in transgenic mice.…”

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confidence: 99%

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Promoter Sequences in the RIβ Subunit Gene of cAMP-dependent Protein Kinase Required for Transgene Expression in Mouse Brain

Clegg

Haugen

Boring³

1996

Journal of Biological Chemistry

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Neural-specific expression of the mouse regulatory type-I␤ (RI␤) subunit gene of cAMP-dependent protein kinase is controlled by a fragment of genomic DNA comprised of a TATA-less promoter flanked by 1.5 kilobases of 5-upstream sequence and a 1.8-kilobase intron. This DNA contains a complex arrangement of transcription factor binding motifs, and previous experiments have shown that many of these are recognized by proteins found in brain nuclear extract. To identify sequences critical for RI␤ expression in functional neurons, we performed a deletion analysis in transgenic mice. Evidence is presented that the GC-rich proximal promoter is responsible for cell type-specific expression in vivo because RI␤ DNA containing as little as 17 base pairs (bp) of 5-upstream sequence was functional in mouse brain. One likely regulatory element coincides with the start of transcription and includes an EGR-1 motif and 3 consecutive SP1 sites within a 21-bp interval. Maximal RI␤ promoter activity required the adjacent 663 bp of 5-upstream DNA where most, but not all, of the regulatory activity was localized between position ؊663 and ؊333. A 37-bp direct repeat lies within this region that contains 2 basic helix-loop-helix binding sites, each of which are overlapped by two steroid hormone receptor half-sites, and a shared AP1 consensus sequence. Intron I sequences were also tested, and deletion of a 388-bp region containing numerous Sp1-like sequences lowered transgene activity significantly. These results have identified specific regions of the RI␤ promoter that are required for the expression of this signal transduction protein in mouse neurons.The variety of neuronal cell types that comprise the mammalian nervous system is determined by highly refined spatial and temporal patterns of gene expression (1, 2). This idea is supported by the restricted expression patterns of numerous transcription factors within the developing nervous system. Members of the homeobox (3, 4), POU domain (5, 6), and bHLH 1 (7, 8) families of DNA binding proteins help initiate the cascades of gene expression that establish region-specific classes of neurons. The diversity of neuronal phenotypes is further enhanced during the life of the organism by stimulusdependent modifications in differentiated neurons. This adaptive plasticity, controlled by various neurotransmitters and cytokines, elicits new patterns of gene expression and long-term changes in cell behavior (9, 10). A better understanding of how neuronal diversity and function is achieved will be facilitated by the identification of the mechanisms that regulate neural-specific gene expression. A mouse gene that we have focused on encodes the regulatory type I␤ (RI␤) subunit of cAMP-dependent protein kinase (PKA) (11). Protein phosphorylation by PKA serves a pivotal role in neuronal function (12)(13)(14). The R subunits of the holoenzyme, of which four genes have been identified, prevent catalysis in the absence of cAMP (15). Each type of regulatory subunit contributes distinct qualities that broade...

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

Promoter Sequences in the RIβ Subunit Gene of cAMP-dependent Protein Kinase Required for Transgene Expression in Mouse Brain

Clegg

Haugen

Boring³

1996

Journal of Biological Chemistry

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“…The Drosophila embryonic peripheral nervous system (PNS) consists of type I and type II neurons Jan, 1993, Jan andJan, 1994). Type I neurons locate within external sensory (ES) and chordotonal (CH) organs.…”

Section: Investigatedmentioning

confidence: 99%

Spatially controlled expression of the Drosophila pseudouridine synthase RluA-1

Wang¹,

Lo²,

Chien³

et al. 2011

Int. J. Dev. Biol.

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Pseudouridine () synthases function in the formation of , the most abundant of the modified RNA residues. All  synthases in E. coli are classified into one of five families according to their sequences. Among them, members of the RluA  synthase family catalyze certain  formations in ribosomal RNA. RluA family members are required for ribosomal assembly and bacterial growth. None of the RluA in multicellular organisms has been studied. In the Drosophila peripheral nervous system, multiple dendritic (MD) neurons are recognized by their dendritic arbors. MD neurons can also be identified by using the enhancer trap line E7-2-36, which expresses the lacZ gene in MD neurons. Here, we show that the P-element of E7-2-36 inserts into the Drosophila RluA-1 gene. RluA-1 is homologous to E. coli RluA family members and is evolutionarily conserved in multicellular organisms. In situ hybridization and immunocytochemistry revealed that RluA-1 is expressed in MD neurons. We investigated the RluA-1 enhancer responsible for MD expression and found that the membrane-tethered green fluorescent protein driven by RluA-1-GAL4 was expressed in the dendritic arbors of MD neurons, confirming that RluA-1 is indeed expressed in MD neurons. Thus, the expression of RluA-1 is spatially controlled during development. KEY WORDS: pseudouridine synthase, multiple dendritic neuronPseudouridine () is the most common modified nucleotide in cellular RNAs (Rozenski et al., 1999).  is synthesized from uridine by  synthases. According to the amino acid sequence,  synthases have been classified into five families: TruD, TruA, TruB, RsuA, and RluA (Kaya and Ofengand, 2003, Koonin, 1996). All  synthases share a conserved active site cleft containing catalytic aspartate (Hamma and Ferre-D'Amare, 2006). In E. coli and yeasts, it is known that each  synthase functions in the synthesis of specific  residues in tRNA or rRNA. For example, the RluA family member RluD in E. coli is responsible for the formation of  residues in rRNA. Lack of RluD causes defects in ribosomal assembly and bacterial growth (Gutgsell et al., 2005). In addition,  synthases may have functions other than  synthesis, such as being an RNA chaperone (Grosshans et al., 2001). In humans, the TruB  synthase dyskerin is involved in an RNP complex, which is required for rRNA processing and telomerase activity as well as  synthesis (Hamma and Ferre-D'Amare, 2006). Mutation in dyskerin causes the human bone marrow failure syndrome dyskeratosis congenita (Heiss et al., 1998). No RluA family  synthases in multicellular organisms have been Int. J. Dev. Biol. 55: 223-227 (2011) doi: 10.1387/ijdb.103112cw Abbreviations used in this paper: PNS, peripheral nervous system; MD, multiple dendritic; , pseudouridine. investigated.The Drosophila embryonic peripheral nervous system (PNS) consists of type I and type II neurons Jan, 1993, Jan andJan, 1994). Type I neurons locate within external sensory (ES) and chordotonal (CH) organs. Each of the type I neurons has one dendrite, whe...

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“…Functional E-boxes are found in the regulatory elements of many lineage-specific genes. Consistently, bHLH are transcription factors acting in various differentiation processes, either as positive or negative regulators, and play key roles in different developmental events like neurogenesis and myogenesis (for review see Jan and Jan, 1993). Drosophila twist is a zygotic developmental gene involved in early mesoderm patterning (Thisse et al, 1987).…”

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confidence: 99%

A twist for survival and cancer progression

2005

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A major obstacle to the expansion of abnormal cells with significant proliferative potential is the induction of programmed cell death. Consequently, oncogene-driven hyperproliferation must be associated with apoptosis inhibition to allow malignant outgrowth. The oncogenic cooperation of N-Myc and Twist-1 in the development of neuroblastoma, the most common and deadly solid tumour of childhood, perfectly illustrates such a process. N-Myc promotes cell proliferation, whereas Twist-1 counteracts its pro-apoptotic properties by knocking-down the ARF/p53 pathway. On the basis of numerous recent studies reporting its overexpression in a variety of human cancers, we discuss in this review the role of Twist-1 as a potent inhibitor of the cell safety programs engaged in response to an abnormal mitogenic activity.

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Functional gene cassettes in development.

Cited by 53 publications

References 38 publications

Promoter Sequences in the RIβ Subunit Gene of cAMP-dependent Protein Kinase Required for Transgene Expression in Mouse Brain

Promoter Sequences in the RIβ Subunit Gene of cAMP-dependent Protein Kinase Required for Transgene Expression in Mouse Brain

Spatially controlled expression of the Drosophila pseudouridine synthase RluA-1

A twist for survival and cancer progression

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