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J A Kennison

Publications and source records attributed to J A Kennison.

At least 19 recordsLinked to original sources
PubMed2001

Essential genes in proximal 3L heterochromatin of Drosophila melanogaster.

We have further characterized essential loci within the centric heterochromatin of the left arm of chromosome 3 (3L) of Drosophila melanogaster, using EMS, radiation and P element mutagenesis. We failed to find any new essential genes, a result that suggests a lower-than-average gene density in this region. Mutations affecting expression of the most proximal gene [lethal 1, l1 or l(3)80Fj] act as dominant suppressors of Polycomb (Pc), behavior which is consistent with a putative trithorax group (trx-G) gene. The third gene to the left of the centromere [lethal 3, l3 or l(3)80Fh] is likely to correspond to verthandi (vtd), a known trx-G gene that plays a role in the regulation of hedgehog (hh) expression and signalling. The intervening gene [lethal 2, l2 or l(3)80Fi] is required throughout development, and mutant alleles have interesting phenotypes; in various allelic combinations that survive, we observe fertility, bristle, wing, eye and cuticle defects.

Animals↗
PubMed2001

Su(z)12, a novel Drosophila Polycomb group gene that is conserved in vertebrates and plants.

In both Drosophila and vertebrates, spatially restricted expression of HOX genes is controlled by the Polycomb group (PcG) repressors. Here we characterize a novel Drosophila PcG gene, Suppressor of zeste 12 (Su(z)12). Su(z)12 mutants exhibit very strong homeotic transformations and Su(z)12 function is required throughout development to maintain the repressed state of HOX genes. Unlike most other PcG mutations, Su(z)12 mutations are strong suppressors of position-effect variegation (PEV), suggesting that Su(z)12 also functions in heterochromatin-mediated repression. Furthermore, Su(z)12 function is required for germ cell development. The Su(z)12 protein is highly conserved in vertebrates and is related to the Arabidopsis proteins EMF2, FIS2 and VRN2. Notably, EMF2 is a repressor of floral homeotic genes. These results suggest that at least some of the regulatory machinery that controls homeotic gene expression is conserved between animals and plants.

Amino Acid Sequence↗
PubMed1999

The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription.

The trithorax group gene brahma (brm) encodes the ATPase subunit of a chromatin-remodeling complex involved in homeotic gene regulation. We report here that brm interacts with another trithorax group gene, osa, to regulate the expression of the Antennapedia P2 promoter. Regulation of Antennapedia by BRM and OSA proteins requires sequences 5' to the P2 promoter. Loss of maternal osa function causes severe segmentation defects, indicating that the function of osa is not limited to homeotic gene regulation. The OSA protein contains an ARID domain, a DNA-binding domain also present in the yeast SWI1 and Drosophila DRI proteins. We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes.

Animals↗
PubMed1999

The Drosophila kismet gene is related to chromatin-remodeling factors and is required for both segmentation and segment identity.

The Drosophila kismet gene was identified in a screen for dominant suppressors of Polycomb, a repressor of homeotic genes. Here we show that kismet mutations suppress the Polycomb mutant phenotype by blocking the ectopic transcription of homeotic genes. Loss of zygotic kismet function causes homeotic transformations similar to those associated with loss-of-function mutations in the homeotic genes Sex combs reduced and Abdominal-B. kismet is also required for proper larval body segmentation. Loss of maternal kismet function causes segmentation defects similar to those caused by mutations in the pair-rule gene even-skipped. The kismet gene encodes several large nuclear proteins that are ubiquitously expressed along the anterior-posterior axis. The Kismet proteins contain a domain conserved in the trithorax group protein Brahma and related chromatin-remodeling factors, providing further evidence that alterations in chromatin structure are required to maintain the spatially restricted patterns of homeotic gene transcription.

Amino Acid Sequence↗
PubMed1998

dMi-2, a hunchback-interacting protein that functions in polycomb repression.

Early in Drosophila embryogenesis, gap gene products directly repress transcription of homeotic (HOX) genes and thereby delimit HOX expression domains. Subsequently, Polycomb-group proteins maintain this repression. Currently, there is no known molecular link between gap and Polycomb-group proteins. Here, dMi-2 is identified as a protein that binds to a domain in the gap protein Hunchback that is specifically required for the repression of HOX genes. Genetic analyses show that dMi-2 participates in both Hunchback and Polycomb repression in vivo. Hence, recruitment of dMi-2 may serve as a link between repression of HOX genes by Hunchback and Polycomb proteins.

Adenosine Triphosphatases↗
PubMed1998

Regulation of the Sex combs reduced gene in Drosophila.

The Sex combs reduced gene of the Antennapedia complex specifics the identities of the anterior thoracic and posterior head segments, including the primordium of the larval salivary gland. The Sex combs reduced transcription unit spans over 30 kb of genomic DNA, with another 40 kb of upstream cis-regulatory sequences. The pattern of Sex combs reduced transcription is set in the early embryo by the segmentation genes and is then maintained by two competing sets of proteins, the Polycomb group and the trithorax group. One of the trithorax group genes required for activation, the brahma gene, encodes an evolutionarily conserved DNA-stimulated ATPase that is part of a large protein complex. This complex facilitates the action of sequence-specific, DNA-binding proteins in regulating target genes, possibly by altering chromatin structure.

Animals↗
PubMed1998

Genetic analysis of brahma: the Drosophila homolog of the yeast chromatin remodeling factor SWI2/SNF2.

The Drosophila brahma (brm) gene encodes an activator of homeotic genes related to the yeast chromatin remodeling factor SWI2/SNF2. Here, we report the phenotype of null and dominant-negative brm mutations. Using mosaic analysis, we found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult. A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATP-binding site of the BRM protein with an arginine. This mutation eliminates brm function in vivo but does not affect assembly of the 2-MD BRM complex. Expression of the dominant-negative BRM protein caused peripheral nervous system defects, homeotic transformations, and decreased viability. Consistent with these findings, the BRM protein is expressed at relatively high levels in nuclei throughout the developing organism. Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein. Domain II is essential for brm function and is required for the assembly or stability of the BRM complex. In spite of its conservation in numerous eukaryotic regulatory proteins, the deletion of the bromodomain of the BRM protein has no discernible phenotype.

Amino Acid Sequence↗
PubMed1997

The Drosophila homeotic gene moira regulates expression of engrailed and HOM genes in imaginal tissues.

moira is a member of the trithorax group of homeotic gene regulators in Drosophila melanogaster. We show that moira is required for the function of multiple homeotic genes of the Antennapedia and bithorax complexes (HOM genes) in most imaginal tissues and that the requirement for moira function is at the level of transcription. moira is also required for transcription of the engrailed segmentation gene in the imaginal wing disc. The abnormalities caused by the loss of moira function in germ cells suggests that at least one other target gene requires moira for normal oogenesis.

Animals↗
PubMed1995

The Polycomb and trithorax group proteins of Drosophila: trans-regulators of homeotic gene function.

The Polycomb and trithorax group genes encode trans-regulators of homeotic gene function in Drosophila. The Polycomb group genes encode transcriptional repressors, while the trithorax group proteins are positive factors required for homeotic gene function. Among the Polycomb group proteins, the POLYCOMB protein has been most extensively characterized. The POLYCOMB protein contains a chromodomain, a conserved domain found in a Drosophila protein with effects on position-effect variegation. Among the trithorax group proteins characterized, the BRAHMA protein appears to be a subunit of a protein complex conserved from yeast to man (the SNF/SWI complex) that modifies chromatin to facilitate the transcriptional activation by gene-specific DNA-binding proteins. The ZESTE protein may help to activate transcription by bringing distant cis-regulatory elements closer to promoter-bound proteins.

Animals↗
PubMed1995

Positional signaling by hedgehog in Drosophila imaginal disc development.

We describe a dominant gain-of-function allele of the segment polarity gene hedgehog. This mutation causes ectopic expression of hedgehog mRNA in the anterior compartment of wing discs, leading to overgrowth of tissue in the anterior of the wing and partial duplication of distal wing structures. The posterior compartment of the wing is unaffected. Other imaginal derivatives are affected, resulting in duplications of legs and antennae and malformations of eyes. In mutant imaginal wing discs, expression of the decapentaplegic gene, which is implicated in the hedgehog signaling pathway, is also perturbed. The results suggest that hedgehog protein acts in the wing as a signal to instruct neighboring cells to adopt fates appropriate to the region of the wing just anterior to the compartmental boundary.

Alleles↗
PubMed1994

Cloning and characterization of the Drosophila melanogaster CDK5 homolog.

The D. melanogaster homolog of mammalian CDK5 has been cloned and its chromosomal location determined. The gene for Cdk5 consists of 4 exons separated by 3 short introns ranging in size from 61-160 bp. Northern blot analysis revealed a single mRNA of approximately 1.6 kb that is expressed at highest levels in the adult fly. The putative amino acid sequence for Drosophila Cdk5 predicts a protein with a mass of approximately 32 kDa that is 77% identical to its mammalian counter-parts. Drosophila Cdk5 gene is located in polytene chromosomal region 52BC of the right arm of chromosome 2. This study provides the framework for a molecular genetic analysis of CDK5 function.

Amino Acid Sequence↗
PubMed1994

Genetic analysis of the brahma gene of Drosophila melanogaster and polytene chromosome subdivisions 72AB.

The brahma gene is required for activation of the homeotic genes of the Antennapedia and bithorax complexes in Drosophila. We have isolated and characterized 21 mutations in brahma. We show that both maternal and zygotic functions of brahma are required during embryogenesis. In addition, the severe abnormalities caused by loss of maternal brahma expression show that the homeotic genes are not the only targets for brahma activation. The complex pattern of interallelic complementation for the 21 brahma alleles suggests that brahama may act as a multimer. In addition to mutations in brahma, we have isolated mutations in four other essential genes within polytene chromosome subdivisions 72AB. Based on a compilation of similar studies that include about 24% of the genome, we estimate that about 3600 genes in Drosophila can mutate to cause recessive lethality, with fewer than 900 additional genes essential only for gametogenesis. We have identified three times more transcripts than lethal complementation groups in 72AB. One transcript in 72AB is the product of the essential arf-like gene and encodes a member of the ARF subfamily of small GTP-binding proteins. Two other transcripts are probably the products of a single gene whose protein products are similar to the catalytic subunits of cAMP-dependent protein kinases.

ADP-Ribosylation Factors↗
PubMed1993

Transcriptional activation of Drosophila homeotic genes from distant regulatory elements.

In Drosophila the genes responsible for specifying segment identity (the homeotic genes) are transcribed in complex patterns during development. Mutations that mimic loss of homeotic gene activity identify cis-acting DNA sequences and trans-acting proteins required for transcriptional activation. Some of the trans-acting proteins may facilitate interactions between cis-regulatory elements and the promoter by bringing together distant chromosomal elements.

Amino Acid Sequence↗
PubMed1992

brahma: a regulator of Drosophila homeotic genes structurally related to the yeast transcriptional activator SNF2/SWI2.

The brahma (brm) gene is required for the activation of multiple homeotic genes in Drosophila. Loss-of-function brm mutations suppress mutations in Polycomb, a repressor of homeotic genes, and cause developmental defects similar to those arising from insufficient expression of the homeotic genes of the Antennapedia and Bithorax complexes. The brm gene encodes a 1638 residue protein that is similar to SNF2/SWI2, a protein involved in transcriptional activation in yeast, suggesting possible models for the role of brm in the transcriptional activation of homeotic genes. In addition, both brm and SNF2 contain a 77 amino acid motif that is found in other Drosophila, yeast, and human regulatory proteins and may be characteristic of a new family of regulatory proteins.

Adenosine Triphosphatases↗
PubMed1992

Trans-regulation of homeotic genes in Drosophila.

Homeotic genes of the Antennapedia and bithorax complexes control Drosophila development by encoding DNA-binding proteins that regulate the transcription of target genes. Because either the presence or absence of these DNA-binding proteins alters development, regulation of the spatial patterns of expression is crucial to normal development. Numerous gene products are required for properly regulated expression of Antennapedia and bithorax complex genes, but few (if any) are dedicated solely to the regulation of these genes. One of the pleiotropic activators of homeotic genes in Drosophila, the brahma gene, encodes a protein similar to a yeast protein that is required for transcriptional activation of multiple tightly regulated genes. Other components of this system may be conserved as well, suggesting that the biochemical basis for induced gene expression in single-celled organisms may have more in common with programmed developmental pathways in multicellular organisms than previously thought.

Animals↗
PubMed1991

The arflike gene encodes an essential GTP-binding protein in Drosophila.

We have identified a Drosophila gene (arflike, arl) encoding a protein that is structurally related (approximately 55% identity) to the ADP-ribosylation factors (ARFs) of yeast and mammals. Biochemical analyses of purified recombinant arl-encoded protein revealed properties similar to the ARF proteins, including the ability to bind and hydrolyze GTP. Clear functional differences between arl and ARF proteins, including a complete lack of ARF activity, suggest that arl is not a functional homolog of ARF. A recessive lethal arl mutation was recovered, demonstrating that the arl locus is an essential gene. We conclude that the arl locus encodes an essential member of the ARF subfamily of small GTP-binding proteins in Drosophila.

ADP-Ribosylation Factors↗
PubMed1989

Reciprocal recombination and the evolution of the ribosomal gene family of Drosophila melanogaster.

The role of reciprocal recombination in the coevolution of the ribosomal RNA gene family on the X and Y chromosomes of Drosophila melanogaster was assessed by determining the frequency and nature of such exchange. In order to detect exchange events within the ribosomal RNA gene family, both flanking markers and restriction fragment length polymorphisms within the tandemly repeated gene family were used. The vast majority of crossovers between flanking markers were within the ribosomal RNA gene region, indicating that this region is a hotspot for heterochromatic recombination. The frequency of crossovers within the ribosomal RNA gene region was approximately 10(-4) in both X/X and X/Y individuals. In conjunction with published X chromosome-specific and Y chromosome-specific sequences and restriction patterns, the data indicate that reciprocal recombination alone cannot be responsible for the observed variation in natural populations.

Animals↗