Integromics: challenges in data integration.
A report on Barnett International's 4th annual Bioinformatics and Data Integration conference, Philadelphia, USA, 7-8 March 2002.
Computational Biology↗
Biomedical subjects
T V Venkatesh
Publications and source records attributed to T V Venkatesh.
Bioinformatics in the pre- and post-genomic eras.
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Computational Biology↗
Cardiac enhancer activity of the homeobox gene tinman depends on CREB consensus binding sites in Drosophila.
The Drosophila homeobox gene tinman plays a critical role in subdividing the early mesoderm. In particular, tinman is absolutely required for formation of the heart and visceral mesoderm. tinman expression is initiated throughout the mesoderm of the trunk region under the control of the bHLH transcription factor encoded by the twist gene, a determinant of all mesoderm. Later, tinman expression is restricted to the dorsal portion of the mesoderm, a process that is directed by decapentaplegic (dpp) whose product (a TGF-beta-related protein) is secreted by the overlaying ectoderm. Further restriction of tinman expression to the cardiac progenitors, in which it will persist throughout development, involves the secreted segmentation gene product encoded by wingless (wg, a Drosophila Wnt gene). Here, we show that strong early expression depends on the synergistic action of an enhancer element at the 5' end of the gene in conjunction with an element in the first intron. Moreover, two distinct enhancer regions are responsible for tinman expression in the heart: one region confers expression in the heart-tube-associated pericardial cells, the other element drives expression in the contractile, myocardial cells. The latter element contains two CREB consensus binding sites that are essential for cardiac-specific expression. genesis 26:55-66, 2000.
Animals↗
Sequence and developmental expression of amphioxus AmphiNk2-1: insights into the evolutionary origin of the vertebrate thyroid gland and forebrain.
We characterized an amphioxus NK-2 homeobox gene (AmphiNk2-1), a homologue of vertebrate Nkx2-1, which is involved in the development of the central nervous system and thyroid gland. At the early neurula stage of amphioxus, AmphiNk2-1 expression is first detected medially in the neural plate. By the mid-neurula stage, expression is localized ventrally in the nerve cord and also begins in the endoderm. During the late neurula stage, the ventral neural expression becomes transiently segmented posteriorly and is then down-regulated except in the cerebral vesicle at the anterior end of the central nervous system. Within the cerebral vesicle AmphiNk2-1 is expressed in a broad ventral domain, probably comprising both the floor plate and basal plate regions; this pattern is comparable to Nkx2-1 expression in the mouse diencephalon. In the anterior part of the gut, expression becomes intense in the endostyle (the right wall of the pharynx), which is the presumed homologue of the vertebrate thyroid gland. More posteriorly, there is transitory expression in the midgut and hindgut. In sum, the present results help to support homologies (1) between the amphioxus endostyle and the vertebrate thyroid gland and (2) between the amphioxus cerebral vesicle and the vertebrate diencephalic forebrain.
Amino Acid Sequence↗
The pioneer gene, apontic, is required for morphogenesis and function of the Drosophila heart.
In an effort to isolate genes required for heart development and to further our understanding of cardiac specification at the molecular level, we screened PlacZ enhancer trap lines for expression in the Drosophila heart. One of the lines generated in this screen, designated B2-2-15, was particularly interesting because of its early pattern of expression in cardiac precursor cells, which is dependent on the homeobox gene tinman, a key determinant of heart development in Drosophila. We isolated and characterized a gene in the vicinity of B2-2-15 that exhibits an identical expression pattern than the reporter gene of the enhancer trap. The product of his gene, apontic (apt; see also "Gellon et al., 1997"), does not appear to have any homology with known genes. apt mutant embryos show distinct abnormalities in heart morphology as early as mid-embryonic stages when the heart tube assembles, in that segments of heart cells (those of myocardial and pericardial identity) are often missing. Most strikingly, however, apt mutant embryos or larvae only develop a much reduced heart rate, perhaps because of defects in the assembly of an intact heart tube and/or because of defects in the function or physiological control of the myocardial cells, which normally mediate heart contractions. These cardiac defects may be the cause of death of these mutants during late embryonic or early larval stages.
Alleles↗
Heart development in Drosophila and vertebrates: conservation of molecular mechanisms.
Vertebrate and insect (Drosophila) hearts look and function quite differently from each other. Nevertheless, during embryogenesis their mesodermal origin and initial assembly into a linear heart tube are comparable in many respects. In the past few years, numerous gene functions have been identified that are utilized by both vertebrates and Drosophila for the specification and differentiation of the heart progenitor cells. These studies have begun with the discovery of the homeobox gene tinman in Drosophila and its vertebrate counterparts. By now, there is also evidence that MEF2 transcription factors and TGF-beta signaling have cardiogenic functions in both these systems. Perhaps in a few years, the GATA and HAND transcription factors and Wnt signaling, which currently only have a demonstrated cardiogenic function in one of the systems, may also be part of this group. One of the pressing but still wide open questions is if the spectrum of targets for these transcription factors and signaling pathways is also conserved.
Animals↗
Dual role for the zeste-white3/shaggy-encoded kinase in mesoderm and heart development of Drosophila.
A Drosophila homolog of the serine/threonine kinase GSK-3 beta, encoded by the zest-white3/shaggy gene (zw3), has been implicated as a maternally provided antagonist of zygotic signaling by the secreted segmentation gene wingless (wg). The wg signal apparently causes a spatially localized inhibition of the ubiquitous repressor function of zw3. This double negative mechanism of signal transduction has been shown to mediate the patterning function of Wg in a number of developmental processes. Although wg is absolutely required for specifying the heart progenitors within the mesoderm of Drosophila, the role of zw3 in this process has been unclear. Here, we present evidence that zw3 has a dual role in mesoderm development: (1) zw3 acts as an antagonist in cardiogenic wg signal transduction, and (2) zw3 also seems to be required to promote positively the formation of a larger mesodermal region, the tinman- and dpp-dependent "dorsal mesoderm," which is a prerequisite not only for cardiogenesis, but also for visceral mesoderm formation. We also demonstrate that a recently identified proximal component of the wg cascade, which is a transcription factor encoded by pangolin/dTCF (dTCF), also seems to mediate wg-dependent cardiogenesis. Further, we present evidence that Notch (N), which opposes wg signaling in other situations, is unlikely to be directly involved in the cardiogenic wg pathway, but seems to have multiple other myogenic functions, one of which is to inhibit mesoderm differentiation altogether, when overexpressed as a constitutively active form.
Animals↗
Characterization and developmental expression of AmphiNk2-2, an NK2 class homeobox gene from Amphioxus. (Phylum Chordata; Subphylum Cephalochordata).
The genome of amphioxus includes AmphiNk2-2, the first gene of the NK2 homeobox class to be demonstrated in any invertebrate deuterostome. AmphiNk2-2 encodes a protein with a TN domain, homeodomain, and NK2-specific domain; on the basis of amino acid identities in these conserved regions, AmphiNk2-2 is a homolog of Drosophila vnd and vertebrate Nkx2-2. During amphioxus development, expression of Amph- iNk2-2 is first detected ventrally in the endoderm of late gastrulae. In neurulae, endodermal expression divides into three domains (the pharynx, midgut, and hindgut), and neural expression commences in two longitudinal bands of cells in the anterior neural tube. These neural tube cells occupy a ventrolateral position on either side of the cerebral vesicle (the probable homolog of the vertebrate diencephalic forebrain). The dynamic expression patterns of AmphiNkx2-2 suggest successive roles, first in regionalizing the endoderm and nervous system and later during differentiation of specific cell types in the gut (possibly peptide endocrine cells) and brain (possibly including axon outgrowth and guidance).
Amino Acid Sequence↗
Large- and small-scale preparation of bacteriophage lambda lysate and DNA.
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Bacteriophage lambda↗
Molecular characterization of the Azotobacter vinelandii recF gene.
The recF gene from Azotobacter vinelandii (Av) has been cloned by complementation in an Escherichia coli (Ec) recF mutant. The sequence of 1568 bp has been determined and analyzed. It showed an open reading frame of 1092 nt coding for a 364-amino-acid (aa) polypeptide. The comparison of the deduced aa sequence of the recF of Av with those of other bacteria has elicited the presence of the four conserved domains thought to be essential for RecF function. A transcriptional fusion of a DNA fragment containing the promoter sequence of recF with the lacZ gene of Ec was constructed and 3-4-fold enhancement of promoter activity was observed upon UV induction.
Amino Acid Sequence↗
How many signals does it take?
Although the genetics of dorsal-ventral polarity which leads to mesoderm formation in Drosophila are understood in considerable detail, subsequent molecular mechanisms involved in patterning the mesoderm primordium into individual mesodermal subtypes are poorly understood. Two papers published recently suggest strongly that an inductive signal from dorsal ectoderm is involved in subdividing the underlying mesoderm, and present evidence that one of the signalling factors is Decapentaplegic (Dpp), a member of the bone morphogenetic protein subgroup of the Transforming Growth Factor-beta (TGF-beta) super family of proteins.
Animals↗
Ribosomal protein S1 and NusA protein complexed to recombination protein beta of phage lambda.
The red genes of bacteriophage lambda specify two proteins, exonuclease and beta protein, which are essential for general recombination of lambda in recA cells. Earlier studies suggested that these proteins form an equimolar complex (C. M. Radding, J. Rosenweig, F. Richards, and E. Cassuto, J. Biol. Chem. 246:2510-2512, 1971). A more recent study indicated that beta protein forms a strong complex with an unknown polypeptide of 70 kDa (K. Muniyappa and C. M. Radding, J. Biol. Chem. 261:7472-7478, 1986). In the present study, in addition to the complex of beta and the 70-kDa protein, a new association of beta protein with a 65-kDa protein was observed. N-terminal sequencing identified these proteins as host-encoded ribosomal protein S1 and transcription terminator protein NusA.
Amino Acid Sequence↗
The Azotobacter vinelandii recA gene: sequence analysis and regulation of expression.
The nucleotide (nt) sequence of the Azotobacter vinelandii recA gene (Av-recA) was determined and compared with the recA sequences from Pseudomonas aeruginosa (Pa-recA), a soil bacterium, and Escherichia coli (Ec-recA), an enteric bacterium. The Av-recA gene and the deduced aa sequence were found to be more similar to their Pa-recA counterparts than to the Ec-recA gene and protein. Expression of Av-recA was found to be autoregulatory. Unlike Ec-recA and Pa-recA, however, expression of Av-recA was weakly enhanced upon DNA damage. In E. coli, expression of an Av-recA::lacZ fusion was poor, but its autoregulation was similar to that of Ec-recA. Av-recA expression, however, could not induce the repair system response in E. coli.
Amino Acid Sequence↗
Cloning and characterization of the Azotobacter vinelandii recA gene and construction of a recA deletion mutant.
The recA gene of Azotobacter vinelandii was isolated from a genomic library by heterologous complementation of an Escherichia coli recA mutation for resistance to UV radiation. The A. vinelandii recA gene was localized on adjacent PstI fragments of 1.3 and 1.7 kb. The cloned A. vinelandii recA gene was functionally analogous to the E. coli recA gene. It was also able to complement the E. coli recA mutation for homologous recombination. A recA deletion mutant of A. vinelandii was constructed. This mutant was sensitive to DNA-damaging agents like UV rays, methyl methane sulfonate (MMS) and nalidixic acid and was deficient in homologous recombination.
Azotobacter↗
Isolation and characterization of a locus from Azospirillum brasilense Sp7 that complements the tumorigenic defect of Agrobacterium tumefaciens chvB mutant.
The chromosomal virulence gene chvB of Agrobacterium tumefaciens is required for pathogenesis. A DNA fragment from the chvB locus can hybridize to DNA from Azospirillum brasilense Sp7. This DNA fragment could restore the tumorigenic activity of the chvB mutant strain A. tumefaciens A1011 towards leaf disks of Nicotiana tabacum. An NH2-terminal open reading frame, 480 codons long, was most likely responsible for the restoration of the tumorigenic activity. The A. brasilense sequence showed good homology with the NH2-terminal region of the ndvB gene of Rhizobium meliloti.
Agrobacterium tumefaciens↗