spen encodes an RNP motif protein that interacts with Hox pathways to repress the development of head-like sclerites in the Drosophila trunk

Development ◽  
1999 ◽  
Vol 126 (23) ◽  
pp. 5373-5385 ◽  
Author(s):  
E.L. Wiellette ◽  
K.W. Harding ◽  
K.A. Mace ◽  
M.R. Ronshaugen ◽  
F.Y. Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Hox Genes ◽  
Protein Isoforms ◽  
Large Protein ◽  
Head Region ◽  
Hox Proteins ◽  
Binding Motifs ◽  
Homeotic Mutant ◽  
Parallel Factor ◽  
Ets Transcription Factor

Drosophila has eight Hox proteins, and they require factors acting in parallel to regulate different segmental morphologies. Here we find that the Drosophila gene split ends (spen), has a homeotic mutant phenotype, and appears to encode such a parallel factor. Our results indicate that spen plays two important segment identity roles. One is to promote sclerite development in the head region, in parallel with Hox genes; the other is to cooperate with Antennapedia and teashirt to suppress head-like sclerite development in the thorax. Our results also indicate that without spen and teashirt functions, Antennapedia loses its ability to specify thoracic identity in the epidermis. spen transcripts encode extraordinarily large protein isoforms (approx. 5,500 amino acids), which are concentrated in embryonic nuclei. Both Spen protein isoforms and Spen-like proteins in other animals possess a clustered repeat of three RNP (or RRM) domains, as well as a conserved motif of 165 amino acids (SPOC domain) at their C-termini. Spen is the only known homeotic protein with RNP binding motifs, which indicates that splicing, transport, or other RNA regulatory steps are involved in the diversification of segmental morphology. Previous studies by Dickson and others (Dickson, B. J., Van Der Straten, A., Dominguez, M. and Hafen, E. (1996). Genetics 142, 163–171) identified spen as a gene that acts downstream of Raf to suppress Raf signaling in a manner similar to the ETS transcription factor Aop/Yan. This raises the intriguing possibility that the Spen RNP protein might integrate signals from both the Raf and Hox pathways.

scholarly journals Hox dosage contributes to flight appendage morphology in Drosophila

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Rachel Paul ◽  
Guillaume Giraud ◽  
Katrin Domsch ◽  
Marilyne Duffraisse ◽  
Frédéric Marmigère ◽  
...  
Keyword(s):  
Drosophila Melanogaster ◽  
Differential Expression ◽  
Hox Genes ◽  
Expression Profiles ◽  
Fruit Fly ◽  
Insect Species ◽  
Wing Morphology ◽  
Hox Proteins ◽  
Spatial Expression ◽  
Flying Insects

AbstractFlying insects have invaded all the aerial space on Earth and this astonishing radiation could not have been possible without a remarkable morphological diversification of their flight appendages. Here, we show that characteristic spatial expression profiles and levels of the Hox genes Antennapedia (Antp) and Ultrabithorax (Ubx) underlie the formation of two different flight organs in the fruit fly Drosophila melanogaster. We further demonstrate that flight appendage morphology is dependent on specific Hox doses. Interestingly, we find that wing morphology from evolutionary distant four-winged insect species is also associated with a differential expression of Antp and Ubx. We propose that variation in the spatial expression profile and dosage of Hox proteins is a major determinant of flight appendage diversification in Drosophila and possibly in other insect species during evolution.

scholarly journals Avoided motifs: short amino acid strings missing from protein datasets

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Pablo Mier ◽  
Miguel A. Andrade-Navarro
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Protein Function ◽  
Large Protein ◽  
New Approach ◽  
Cellular Context ◽  
Human Proteins ◽  
Context Specific ◽  
Protein Datasets

Abstract According to the amino acid composition of natural proteins, it could be expected that all possible sequences of three or four amino acids will occur at least once in large protein datasets purely by chance. However, in some species or cellular context, specific short amino acid motifs are missing due to unknown reasons. We describe these as Avoided Motifs, short amino acid combinations missing from biological sequences. Here we identify 209 human and 154 bacterial Avoided Motifs of length four amino acids, and discuss their possible functionality according to their presence in other species. Furthermore, we determine two Avoided Motifs of length three amino acids in human proteins specifically located in the cytoplasm, and two more in secreted proteins. Our results support the hypothesis that the characterization of Avoided Motifs in particular contexts can provide us with information about functional motifs, pointing to a new approach in the use of molecular sequences for the discovery of protein function.

NonO, a non-POU-domain-containing, octamer-binding protein, is the mammalian homolog of Drosophila nonAdiss

1993 ◽  
Vol 13 (9) ◽  
pp. 5593-5603
Author(s):  
Y S Yang ◽  
J H Hanke ◽  
L Carayannopoulos ◽  
C M Craft ◽  
J D Capra ◽  
...  
Keyword(s):  
Amino Acids ◽  
Dna Binding ◽  
Protein Binding ◽  
Aromatic Amino Acids ◽  
Courtship Song ◽  
Dna Binding Domain ◽  
Binding Motifs ◽  
Dna And Rna ◽  
Pou Domain ◽  
A Site

We have cloned the ubiquitous form of an octamer-binding, 60-kDa protein (NonO) that appears to be the mammalian equivalent of the Drosophila visual and courtship song behavior protein, no-on-transient A/dissonance (nonAdiss). A region unprecedently rich in aromatic amino acids containing two ribonuclear protein binding motifs is highly conserved between the two proteins. A ubiquitous form of NonO is present in all adult tissues, whereas lymphocytes and retina express unique forms of NonO mRNA. The ubiquitous form contains a potential helix-turn-helix motif followed by a highly charged region but differs from prototypic octamer-binding factors by lacking the POU DNA-binding domain. In addition to its conventional octamer duplex-binding, NonO binds single-stranded DNA and RNA at a site independent of the duplex site.

Homeotic response elements are tightly linked to tissue-specific elements in a transcriptional enhancer of the teashirt gene

Development ◽  
1995 ◽  
Vol 121 (9) ◽  
pp. 2799-2812 ◽  
Author(s):  
A. McCormick ◽  
N. Core ◽  
S. Kerridge ◽  
M.P. Scott
Keyword(s):  
Transcriptional Activation ◽  
Target Genes ◽  
Hox Genes ◽  
Zinc Finger Protein ◽  
Cell Types ◽  
Transcriptional Enhancer ◽  
Hox Proteins ◽  
Tissue Specific ◽  
Conserved Sequences

Along the anterior-posterior axis of animal embryos, the choice of cell fates, and the organization of morphogenesis, is regulated by transcription factors encoded by clustered homeotic or ‘Hox’ genes. Hox genes function in both epidermis and internal tissues by regulating the transcription of target genes in a position- and tissue-specific manner. Hox proteins can have distinct targets in different tissues; the mechanisms underlying tissue and homeotic protein specificity are unknown. Light may be shed by studying the organization of target gene enhancers. In flies, one of the target genes is teashirt (tsh), which encodes a zinc finger protein. tsh itself is a homeotic gene that controls trunk versus head development. We identified a tsh gene enhancer that is differentially activated by Hox proteins in epidermis and mesoderm. Sites where Antennapedia (Antp) and Ultrabithorax (Ubx) proteins bind in vitro were mapped within evolutionarily conserved sequences. Although Antp and Ubx bind to identical sites in vitro, Antp activates the tsh enhancer only in epidermis while Ubx activates the tsh enhancer in both epidermis and in somatic mesoderm. We show that the DNA elements driving tissue-specific transcriptional activation by Antp and Ubx are separable. Next to the homeotic protein-binding sites are extensive conserved sequences likely to control tissue activation by different homeodomain proteins. We propose that local interactions between homeotic proteins and other factors effect activation of targets in proper cell types.

scholarly journals Hoxa1 and TALE proteins display cross-regulatory interactions and form a combinatorial binding code on Hoxa1 targets

2016 ◽  
Author(s):  
Bony De Kumar ◽  
Hugo J. Parker ◽  
Ariel Paulson ◽  
Mark E. Parrish ◽  
Irina Pushel ◽  
...  
Keyword(s):  
Es Cells ◽  
Hox Proteins ◽  
Binding Motifs ◽  
Functional Roles ◽  
Regulatory Interactions ◽  
Mouse Es Cells ◽  
Genome Wide ◽  
A Genome ◽  
Combinatorial Interactions ◽  
Insight Into

AbstractHoxa1 has diverse functional roles in differentiation and development. We have identified and characterized properties of regions bound by Hoxa1 on a genome-wide basis in differentiating mouse ES cells. Hoxa1 bound regions are enriched for clusters of consensus binding motifs for Hox, Pbx and Meis and many display co-occupancy of Pbx and Meis. Pbx and Meis are members of the TALE family and genome-wide analysis of multiple TALE members (Pbx, Meis, TGIF, Prep1 and Prep2) show that nearly all Hoxa1 targets display occupancy of one or more TALE members. The combinatorial binding patterns of TALE proteins defines distinct classes of Hoxa1 targets and indicates a role as cofactors in modulating the specificity of Hox proteins. We also discovered extensive auto- and cross-regulatory interactions among the Hoxa1 and TALE genes. This study provides new insight into a regulatory network involving combinatorial interactions between Hoxa1 and TALE proteins.

Investigation of Optimum Conformations and Structure Analysis of RL and LR Nests using Ramachandran Plot

2015 ◽  
pp. 209-224
Author(s):  
Sumukh Deshpande ◽  
Saikat Kumar Basu ◽  
Pooja Purohit
Keyword(s):  
Amino Acids ◽  
Ring Structure ◽  
Ramachandran Plot ◽  
Binding Motifs ◽  
Automated Algorithm ◽  
Automation And Control ◽  
The Common ◽  
And Control ◽  
Common Anion ◽  
Unique Application

We have surveyed polypeptides with the optimal conformations of nests which are the common anion-binding motifs comprising 8% of the amino acids which are characterized by a structural depression or a hole. Using automated bioinformatics algorithm, novel ring structure of the nest has been found. Using automated algorithm, models of polypeptides were made in-silico (computationally) and oxygen atoms are inserted along the extension of the NH groups. These sophisticated algorithms allow insertion of atoms along the NH group at the correct distance which causes extension of the group thus forming hydrogen bond. Optimal conformations of these structures are found from these customized models. This study chapter provides a demonstration of an important discovery of optimum conformations of RL and LR nests by the use of sophisticated bioinformatics automation pipeline and a unique application of automation and control in bioinformatics.

scholarly journals Binding Motifs in the Naked Complexes of Target Amino Acids with an Excerpt of Antitumor Active Biomolecule: An Ion Vibrational Spectroscopy Assay

2020 ◽  
Author(s):  
Barbara Chiavarino ◽  
Rajeev K. Sinha ◽  
Maria Elisa Crestoni ◽  
Davide Corinti ◽  
Antonello Filippi ◽  
...  
Keyword(s):  
Amino Acids ◽  
Vibrational Spectroscopy ◽  
Binding Motifs

Fusion to Vp16 Converts MEIS1 into an Oncoprotein That Immortalizes Progenitors and Causes AML in the Absence of Coexpressed Hox Genes: Hoxa7 and Hoxa9 Induced Further Stem Cell Gene Transcription in Vp16MEIS1 Progenitors.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 662-662
Author(s):  
Gang G. Wang ◽  
Martina P. Pasillas ◽  
Mark P. Kamps
Keyword(s):  
Stem Cell ◽  
Gene Transcription ◽  
Myeloid Leukemia ◽  
Hox Genes ◽  
Gene Activation ◽  
Transactivation Domain ◽  
Hox Proteins ◽  
Bona Fide ◽  
Essential Function ◽  
Cell Gene

Abstract MEIS1 and Hoxa9 are homeobox transcription factors that promote self-renewal in hematopoietic progenitors. MEIS1 does not induce leukemia, but cooperates strongly with Hoxa9 to produce acute myeloid leukemia (AML). Previously, we demonstrated that Hoxa9 blocks differentiation of myeloid progenitors that do not express MEIS1 and do not induce leukemic. Coexpression of MEIS1 causes transcription of genes that segregate with the leukemia-initiating subset of human AML blasts, such as CD34 and FLT3. We designate these genes as leukemic stem cell genes, or LSC genes. MEIS1 promoted LCS gene transcription by a mechanism that requires interaction with PBX and DNA, and that also requires a short MEIS1 C-terminal transactivation domain (CTD). Here we use a dominant transactivating or transrepressing form of MEIS1 to determine whether the activation or repression function of Pbx:MEIS1 complexes is sufficient to cause myeloid leukemia in combination with coexpressed Hoxa9. Surprisingly, fusion of MEIS1 to the Vp16 transactivation domain (but not the engrailed transrepression domain) produced an autonomous oncoprotein that immortalized progenitors and caused myeloid leukemias without the need for coexpressed exogenous or endogenous Hox genes. Like MEIS1, Vp16MEIS1 required binding to Pbx and DNA for immortalization; however, the CTD was not necessary in the context of Vp16MEIS1. This suggests that the CTD participates in target gene activation in AML blasts, a function replaced by Vp16 in its absence. Retroviral expression of Hoxa9 or Hoxa7 induced a further, strong, transcriptional upregulation of LSC genes in Vp16MEIS1 progenitors and elevated their leukemic potential to the level of bona fide AML blasts. These data suggest that transactivation is the essential function of Pbx:MEIS1 complexes in AML, and that HOX proteins cooperate with Pbx:MEIS1 complexes to activate transcription of early progenitor genes whose expression is required for human AML.

scholarly journals The Type IVa Pilus Machinery Is Recruited to Sites of Future Cell Division

mBio ◽  
2017 ◽  
Vol 8 (1) ◽  
Author(s):  
Tyson Carter ◽  
Ryan N. C. Buensuceso ◽  
Stephanie Tammam ◽  
Ryan P. Lamers ◽  
Hanjeong Harvey ◽  
...  
Keyword(s):  
Cell Division ◽  
Bacterial Cell ◽  
Protein Complexes ◽  
Cell Envelope ◽  
Assembly System ◽  
Physical Barrier ◽  
Large Protein ◽  
Binding Motifs ◽  
Daughter Cells ◽  
Cell Envelopes

ABSTRACT Type IVa pili (T4aP) are ubiquitous microbial appendages used for adherence, twitching motility, DNA uptake, and electron transfer. Many of these functions depend on dynamic assembly and disassembly of the pilus by a megadalton-sized, cell envelope-spanning protein complex located at the poles of rod-shaped bacteria. How the T4aP assembly complex becomes integrated into the cell envelope in the absence of dedicated peptidoglycan (PG) hydrolases is unknown. After ruling out the potential involvement of housekeeping PG hydrolases in the installation of the T4aP machinery in Pseudomonas aeruginosa, we discovered that key components of inner (PilMNOP) and outer (PilQ) membrane subcomplexes are recruited to future sites of cell division. Midcell recruitment of a fluorescently tagged alignment subcomplex component, mCherry-PilO, depended on PilQ secretin monomers—specifically, their N-terminal PG-binding AMIN domains. PilP, which connects PilO to PilQ, was required for recruitment, while PilM, which is structurally similar to divisome component FtsA, was not. Recruitment preceded secretin oligomerization in the outer membrane, as loss of the PilQ pilotin PilF had no effect on localization. These results were confirmed in cells chemically blocked for cell division prior to outer membrane invagination. The hub protein FimV and a component of the polar organelle coordinator complex—PocA—were independently required for midcell recruitment of PilO and PilQ. Together, these data suggest an integrated, energy-efficient strategy for the targeting and preinstallation—rather than retrofitting—of the T4aP system into nascent poles, without the need for dedicated PG-remodeling enzymes. IMPORTANCE The peptidoglycan (PG) layer of bacterial cell envelopes has limited porosity, representing a physical barrier to the insertion of large protein complexes involved in secretion and motility. Many systems include dedicated PG hydrolase components that create space for their insertion, but the ubiquitous type IVa pilus (T4aP) system lacks such an enzyme. Instead, we found that components of the T4aP system are recruited to future sites of cell division, where they could be incorporated into the cell envelope during the formation of new poles, eliminating the need for PG hydrolases. Targeting depends on the presence of septal PG-binding motifs in specific components, as removal of those motifs causes delocalization. This preinstallation strategy for the T4aP assembly system would ensure that both daughter cells are poised to extrude pili from new poles as soon as they separate from one another. IMPORTANCE The peptidoglycan (PG) layer of bacterial cell envelopes has limited porosity, representing a physical barrier to the insertion of large protein complexes involved in secretion and motility. Many systems include dedicated PG hydrolase components that create space for their insertion, but the ubiquitous type IVa pilus (T4aP) system lacks such an enzyme. Instead, we found that components of the T4aP system are recruited to future sites of cell division, where they could be incorporated into the cell envelope during the formation of new poles, eliminating the need for PG hydrolases. Targeting depends on the presence of septal PG-binding motifs in specific components, as removal of those motifs causes delocalization. This preinstallation strategy for the T4aP assembly system would ensure that both daughter cells are poised to extrude pili from new poles as soon as they separate from one another.

scholarly journals Both Pbx1 and E2A-Pbx1 bind the DNA motif ATCAATCAA cooperatively with the products of multiple murine Hox genes, some of which are themselves oncogenes.

1995 ◽  
Vol 15 (7) ◽  
pp. 3786-3795 ◽  
Author(s):  
Q Lu ◽  
P S Knoepfler ◽  
J Scheele ◽  
D D Wright ◽  
M P Kamps
Keyword(s):  
Dna Binding ◽  
Target Genes ◽  
Hox Genes ◽  
Physical Interaction ◽  
Homeodomain Protein ◽  
Structural Development ◽  
Cell Leukemia ◽  
Homeodomain Proteins ◽  
Hox Proteins

E2A-PBX1 is the oncogene produced at the t(1;19) chromosomal breakpoint of pediatric pre-B-cell leukemia. Expression of E2A-Pbx1 induces fibroblast transformation and myeloid and T-cell leukemia in mice and arrests differentiation of granulocyte macrophage colony-stimulating factor-dependent myeloblasts in cultured marrow. Recently, the Drosophila melanogaster protein Exd, which is highly related to Pbx1, was shown to bind DNA cooperatively with the Drosophila homeodomain proteins Ubx and Abd-A. Here, we demonstrate that the normal Pbx1 homeodomain protein, as well as its oncogenic derivative, E2A-Pbx1, binds the DNA sequence ATCAATCAA cooperatively with the murine Hox-A5, Hox-B7, Hox-B8, and Hox-C8 homeodomain proteins, which are themselves known oncoproteins, as well as with the Hox-D4 homeodomain protein. Cooperative binding to ATCAATCAA required the homeodomain-dependent DNA-binding activities of both Pbx1 and the Hox partner. In cotransfection assays, Hox-B8 suppressed transactivation by E2A-Pbx1. These results suggest that (i) Pbx1 may participate in the normal regulation of Hox target gene transcription in vivo and therein contribute to aspects of anterior-posterior patterning and structural development in vertebrates, (ii) that E2A-Pbx1 could abrogate normal differentiation by altering the transcriptional regulation of Hox target genes in conjunction with Hox proteins, and (iii) that the oncogenic mechanism of certain Hox proteins may require their physical interaction with Pbx1 as a cooperating, DNA-binding partner.

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