Loss- and gain-of-function mutations show a polycomb group function for Ring1A in mice

Development ◽  
2000 ◽  
Vol 127 (23) ◽  
pp. 5093-5100 ◽  
Author(s):  
M. del Mar Lorente ◽  
C. Marcos-Gutierrez ◽  
C. Perez ◽  
J. Schoorlemmer ◽  
A. Ramirez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Gene Dosage ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Genetic Evidence ◽  
Molecular Evidence ◽  
Group Function

The products of the Polycomb group (PcG) of genes act as transcriptional repressors involved in the maintenance of homeotic gene expression patterns throughout development, from flies to mice. Biochemical and molecular evidence suggests that the mouse Ring1A gene is a member of the PcG of genes. However, genetic evidence is needed to establish PcG function for Ring1A, since contrary to all other murine PcG genes, there is no known Drosophila PcG gene encoding a homolog of the Ring1A protein. To study Ring1A function we have generated a mouse line lacking Ring1A and mouse lines overexpressing Ring1A. Both Ring1A(−/−)and Ring1A(+/−) mice show anterior transformations and other abnormalities of the axial skeleton, which indicates an unusual sensitivity of axial skeleton patterning to Ring1A gene dosage. Ectopic expression of Ring1A also results in dose-dependent anterior transformations of vertebral identity, many of which, interestingly, are shared by Ring1A(−/−) mice. In contrast, the alterations of Hox gene expression observed in both type of mutant mice are subtle and involve a reduced number of Hox genes. Taken together, these results provide genetic evidence for a PcG function of the mouse Ring1A gene.

Genetic interactions and dosage effects of Polycomb group genes in mice

Development ◽  
1998 ◽  
Vol 125 (18) ◽  
pp. 3543-3551 ◽  
Author(s):  
S. Bel ◽  
N. Core ◽  
M. Djabali ◽  
K. Kieboom ◽  
N. Van der Lugt ◽  
...  
Keyword(s):  
Hox Genes ◽  
Expression Patterns ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Genetic Interactions ◽  
Homeotic Gene ◽  
Polycomb Group Genes ◽  
Dosage Effects ◽  
Somitic Mesoderm ◽  
Homeotic Gene Expression

In Drosophila and mouse, Polycomb group genes are involved in the maintenance of homeotic gene expression patterns throughout development. Here we report the skeletal phenotypes of compound mutants for two Polycomb group genes bmi1 and M33. We show that mice deficient for both bmi1 and M33 present stronger homeotic transformations of the axial skeleton as compared to each single Polycomb group mutant, indicating strong dosage interactions between those two genes. These skeletal transformations are accompanied with an enhanced shift of the anterior limit of expression of several Hox genes in the somitic mesoderm. Our results demonstrate that in mice the Polycomb group genes act in synergy to control the nested expression pattern of some Hox genes in somitic mesodermal tissues during development.

scholarly journals Polycomb requires Tcp-1η chaperonin for maintaining gene silencing inDrosophila

2021 ◽  
Author(s):  
Najma Shaheen ◽  
Jawad Akhtar ◽  
Zain Umer ◽  
Muhammad Haider Farooq Khan ◽  
Murtaza Saleem ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Fate ◽  
Molecular Interaction ◽  
Hox Genes ◽  
Genetic Interaction ◽  
Expression Patterns ◽  
Polycomb Group ◽  
Gene Expression Patterns ◽  
Specific Gene ◽  
Cellular Memory

AbstractIn metazoans, heritable states of cell type specific gene expression patterns linked with specialization of various cell types constitute transcriptional cellular memory. Evolutionarily conserved Polycomb group (PcG) and trithorax group (trxG) proteins contribute to the transcriptional cellular memory by maintaining heritable patterns of repressed and active expression states, respectively. Although chromatin structure and modifications appear to play a fundamental role in maintenance of repression by PcG, the precise targeting mechanism and the specificity factors that bind PcG complexes to a defined region in chromosomes remain elusive. Here we report a serendipitous discovery that uncovers a direct molecular interaction between Polycomb (PC) and TCP-1 Ring Complex (TRiC) chaperonin subunit, Tcp-1η inDrosophila. Tcp-1η interacts with PC at chromatin to maintain repressed states of homeotic and non-homeotic targets of PcG, which supports a strong genetic interaction observed betweenPcandTcp-1ηmutants. Depletion of Tcp-1η results in dissociation of PC from chromatin and redistribution of an abundant amount of PC in cytoplasm. We propose that Tcp-1η is an important modulator of PC, which helps PC recruitment at chromatin and compromising Tcp-1η can directly influence an evolutionary highly conserved epigenetic network that supervises the appropriate cellular identities during development and homoeostasis of an organism.Significance StatementSilencing of key developmental genes, e.g, Hox genes, by PcG is a hallmark of differential gene expression patterns associated with cell fate determination. Here we describe a previously unknown molecular and genetic interaction of Polycomb (PC) with Tcp-1η subunit of TRiC chaperonin complex inDrosophila. Compromising Tcp-1η function results in de-repression of PcG targets and a concomitant loss of PC from chromatin. Moreover, depletion of Tcp-1η leads to redistribution of PC in cytoplasm. Molecular interaction of PC with Tcp-1η highlights a novel factor which helps PC recruitment at chromatin. We propose that Tcp-1η chaperonin is one of the specificity factors and part of the targeting mechanism that binds PC to specific regions on chromosomes.

Analysis of Hox gene expression in the chick limb bud

Development ◽  
1996 ◽  
Vol 122 (5) ◽  
pp. 1449-1466 ◽  
Author(s):  
C.E. Nelson ◽  
B.A. Morgan ◽  
A.C. Burke ◽  
E. Laufer ◽  
E. DiMambro ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Proliferation ◽  
Sonic Hedgehog ◽  
Hind Limb ◽  
Hox Genes ◽  
Expression Patterns ◽  
Limb Bud ◽  
Posterior Portion ◽  
Hox Gene ◽  
Hoxd Gene

The vertebrate Hox genes have been shown to be important for patterning the primary and secondary axes of the developing vertebrate embryo. The function of these genes along the primary axis of the embryo has been generally interpreted in the context of positional specification and homeotic transformation of axial structures. The way in which these genes are expressed and function during the development of the secondary axes, particularly the limb, is less clear. In order to provide a reference for understanding the role of the Hox genes in limb patterning, we isolated clones of 23 Hox genes expressed during limb development, characterized their expression patterns and analyzed their regulation by the signalling centers which pattern the limb. The expression patterns of the Abd-B-related Hoxa and Hoxd genes have previously been partially characterized; however, our study reveals that these genes are expressed in patterns more dynamic and complex than generally appreciated, only transiently approximating simple, concentric, nested domains. Detailed analysis of these patterns suggests that the expression of each of the Hoxa and Hoxd genes is regulated in up to three independent phases. Each of these phases appears to be associated with the specification and patterning of one of the proximodistal segments of the limb (upper arm, lower arm and hand). Interestingly, in the last of these phases, the expression of the Hoxd genes violates the general rule of spatial and temporal colinearity of Hox gene expression with gene order along the chromosome. In contrast to the Abd-B-related Hoxa and Hoxd genes, which are expressed in both the fore and hind limbs, different sets of Hoxc genes are expressed in the two limbs. There is a correlation between the relative position of these genes along the chromosome and the axial level of the limb bud in which they are expressed. The more 3′ genes are expressed in the fore limb bud while the 5′ genes are expressed in the hind limb bud; intermediate genes are transcribed in both limbs. However, there is no clear correlation between the relative position of the genes along the chromosome and their expression domains within the limb. With the exception of Hoxc-11, which is transcribed in a posterior portion of the hind limb, Hoxc gene expression is restricted to the anterior/proximal portion of the limb bud. Importantly, comparison of the distributions of Hoxc-6 RNA and protein products reveals posttranscriptional regulation of this gene, suggesting that caution must be exercised in interpreting the functional significance of the RNA distribution of any of the vertebrate Hox genes. To understand the genesis of the complex patterns of Hox gene expression in the limb bud, we examined the propagation of Hox gene expression relative to cell proliferation. We find that shifts in Hox gene expression cannot be attributed to passive expansion due to cell proliferation. Rather, phase-specific Hox gene expression patterns appear to result from a context-dependent response of the limb mesoderm to Sonic hedgehog. Sonic hedgehog (the patterning signal from the Zone of Polarizing Activity) is known to be able to activate Hoxd gene expression in the limb. Although we find that Sonic hedgehog is capable of initiating and polarizing Hoxd gene expression during both of the latter two phases of Hox gene expression, the specific patterns induced are not determined by the signal, but depend upon the temporal context of the mesoderm receiving the signal. Misexpression of Sonic hedgehog also reveals that Hoxb-9, which is normally excluded from the posterior mesenchyme of the leg, is negatively regulated by Sonic hedgehog and that Hoxc-11, which is expressed in the posterior portion of the leg, is not affected by Sonic hedgehog and hence is not required to pattern the skeletal elements of the lower leg.

Sonic hedgehog is not required for polarising activity in the Doublefoot mutant mouse limb bud

Development ◽  
1998 ◽  
Vol 125 (3) ◽  
pp. 351-357 ◽  
Author(s):  
C. Hayes ◽  
J.M. Brown ◽  
M.F. Lyon ◽  
G.M. Morriss-Kay
Keyword(s):  
Gene Expression ◽  
Limb Development ◽  
Target Genes ◽  
Anterior Part ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Mutant Gene ◽  
Limb Bud ◽  
Active Constituent ◽  
Limb Buds

The mouse mutant Doublefoot (Dbf) shows preaxial polydactyly of all four limbs. We have analysed limb development in this mutant with respect to morphogenesis, gene expression patterns and ectopic polarising activity. The results reveal a gain-of-function mutation at a locus that mediates pattern formation in the developing limb. Shh expression is identical with that of wild-type embryos, i.e. there is no ectopic expression. However, mesenchyme from the anterior aspects of Dbf/+ mutant limb buds, when transplanted to the anterior side of chick wing buds, induces duplication of the distal skeletal elements. Mid-distal mesenchymal transplants from early, but not later, Dbf/+ limb buds are also able to induce duplication. This demonstration of polarising activity in the absence of Shh expression identifies the gene at the Dbf locus as a new genetic component of the Shh signalling pathway, which (at least in its mutated form) is able to activate signal transduction independently of Shh. The mutant gene product is sufficient to fulfil the signalling properties of Shh including upregulation of the direct Shh target genes Ptc and Gli, and induction of the downstream target genes Bmp2, Fgf4 and Hoxd13. The expression domains of all these genes extend from their normal posterior domains into the anterior part of the limb bud without being focused on a discrete ectopic site. These observations dissociate polarising activity from Shh gene expression in the Dbf/+ limb bud. We suggest that the product of the normal Dbf gene is a key active constituent of the polarising region, possibly acting in the extracellular compartment.

scholarly journals Dorsoventral decoupling of Hox gene expression underpins the diversification of molluscs

2019 ◽  
Vol 117 (1) ◽  
pp. 503-512 ◽  
Author(s):  
Pin Huan ◽  
Qian Wang ◽  
Sujian Tan ◽  
Baozhong Liu
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Dorsal Side ◽  
The Other ◽  
Strongly Correlated ◽  
Expression Data ◽  
Shell Formation ◽  
Hox Gene ◽  
Evolutionary Diversification

In contrast to the Hox genes in arthropods and vertebrates, those in molluscs show diverse expression patterns with differences reported among lineages. Here, we investigate 2 phylogenetically distant molluscs, a gastropod and a polyplacophoran, and show that the Hox expression in both species can be divided into 2 categories. The Hox expression in the ventral ectoderm generally shows a canonical staggered pattern comparable to the patterns of other bilaterians and likely contributes to ventral patterning, such as neurogenesis. The other category of Hox expression on the dorsal side is strongly correlated with shell formation and exhibits lineage-specific characteristics in each class of mollusc. This generalized model of decoupled dorsoventral Hox expression is compatible with known Hox expression data from other molluscan lineages and may represent a key characteristic of molluscan Hox expression. These results support the concept of widespread staggered Hox expression in Mollusca and reveal aspects that may be related to the evolutionary diversification of molluscs. We propose that dorsoventral decoupling of Hox expression allowed lineage-specific dorsal and ventral patterning, which may have facilitated the evolution of diverse body plans in different molluscan lineages.

scholarly journals A plethora of plant serine/arginine-rich proteins: redundancy or evolution of novel gene functions?

2004 ◽  
Vol 32 (4) ◽  
pp. 561-564 ◽  
Author(s):  
M. Kalyna ◽  
A. Barta
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Environmental Control ◽  
Expression Patterns ◽  
Ectopic Expression ◽  
Sr Proteins ◽  
Sr Protein ◽  
Duplication Events ◽  
Intron Recognition ◽  
Alternatively Spliced

Precursor-mRNA (pre-mRNA) processing is an important step in gene expression and its regulation leads to the expansion of the gene product repertoire. SR (serine-arginine)-rich proteins are key players in intron recognition and spliceosome assembly and significantly contribute to the alternative splicing process. Due to several duplication events, at least 19 SR proteins are present in the Arabidopsis genome, which is almost twice as many as in humans. They fall into seven different subfamilies, three of them homologous with metazoan splicing factors, whereas the other four seem to be specific for plants. The current results show that most of the duplicated genes have different spatiotemporal expression patterns indicating functional diversification. Interestingly, most of the SR protein genes are alternatively spliced and in some cases this process was shown to be under developmental and/or environmental control. This might greatly influence gene expression of target genes as also exemplified by ectopic expression studies of particular SR proteins.

scholarly journals Characterization of Interactions between the Mammalian Polycomb-Group Proteins Enx1/EZH2 and EED Suggests the Existence of Different Mammalian Polycomb-Group Protein Complexes

1998 ◽  
Vol 18 (6) ◽  
pp. 3586-3595 ◽  
Author(s):  
Richard G. A. B. Sewalt ◽  
Johan van der Vlag ◽  
Marco J. Gunster ◽  
Karien M. Hamer ◽  
Jan L. den Blaauwen ◽  
...  
Keyword(s):  
Gene Expression ◽  
Protein Complexes ◽  
Expression Patterns ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Sex Combs ◽  
Group Protein ◽  
Nuclear Domains ◽  
Z Protein

ABSTRACT In Drosophila melanogaster, thePolycomb-group (PcG) andtrithorax-group (trxG) genes have been identified as repressors and activators, respectively, of gene expression. Both groups of genes are required for the stable transmission of gene expression patterns to progeny cells throughout development. Several lines of evidence suggest a functional interaction between the PcG and trxG proteins. For example, genetic evidence indicates that the enhancer of zeste [E(z)] gene can be considered both a PcG and a trxGgene. To better understand the molecular interactions in which the E(z) protein is involved, we performed a two-hybrid screen with Enx1/EZH2, a mammalian homolog of E(z), as the target. We report the identification of the human EED protein, which interacts with Enx1/EZH2. EED is the human homolog ofeed, a murine PcG gene which has extensive homology with the Drosophila PcG gene extra sex combs(esc). Enx1/EZH2 and EED coimmunoprecipitate, indicating that they also interact in vivo. However, Enx1/EZH2 and EED do not coimmunoprecipitate with other human PcG proteins, such as HPC2 and BMI1. Furthermore, unlike HPC2 and BMI1, which colocalize in nuclear domains of U-2 OS osteosarcoma cells, Enx1/EZH2 and EED do not colocalize with HPC2 or BMI1. Our findings indicate that Enx1/EZH2 and EED are members of a class of PcG proteins that is distinct from previously described human PcG proteins.

scholarly journals Impact of transposable elements on methylation and gene expression across natural accessions of Brachypodium distachyon

2020 ◽  
Author(s):  
Michele Wyler ◽  
Christoph Stritt ◽  
Jean-Claude Walser ◽  
Célia Baroux ◽  
Anne C. Roulin
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Transposable Elements ◽  
Plant Species ◽  
Brachypodium Distachyon ◽  
Expression Patterns ◽  
Small Subset ◽  
Molecular Evidence ◽  
Specific Gene ◽  
Plant Genomes

AbstractTransposable elements (TEs) constitute a large fraction of plant genomes and are mostly present in a transcriptionally silent state through repressive epigenetic modifications such as DNA methylation. TE silencing is believed to influence the regulation of adjacent genes, possibly as DNA methylation spreads away from the TE. Whether this is a general principle or a context-dependent phenomenon is still under debate, pressing for studying the relationship between TEs, DNA methylation and nearby gene expression in additional plant species. Here we used the grass Brachypodium distachyon as a model and produced DNA methylation and transcriptome profiles for eleven natural accessions. In contrast to what is observed in Arabidopsis thaliana, we found that TEs have a limited impact on methylation spreading and that only few TE families are associated to a low expression of their adjacent genes. Interestingly, we found that a subset of TE insertion polymorphisms is associated with differential gene expression across accessions. Thus, although not having a global impact on gene expression, distinct TE insertions may contribute to specific gene expression patterns in B. distachyon.Significance statementTransposable elements (TEs) are a major component of plant genomes and a source of genetic and epigenetic innovations underlying adaptation to changing environmental conditions. Yet molecular evidence linking TE silencing and nearby gene expression are lacking for many plant species. We show that in the model grass Brachypodium DNA methylation spreads over very short distances around TEs, with an influence on gene expression for a small subset of TE families.

Exploring the myriapod body plan: expression patterns of the ten Hox genes in a centipede

Development ◽  
2002 ◽  
Vol 129 (5) ◽  
pp. 1225-1238 ◽  
Author(s):  
Cynthia L. Hughes ◽  
Thomas C. Kaufman
Keyword(s):  
Gene Expression ◽  
Hox Genes ◽  
Expression Patterns ◽  
Body Plan ◽  
Phylogenetic Position ◽  
The Novel ◽  
Fushi Tarazu ◽  
Hox Gene ◽  
Insight Into ◽  
Gaining Insight

The diversity of the arthropod body plan has long been a fascinating subject of study. A flurry of recent research has analyzed Hox gene expression in various arthropod groups, with hopes of gaining insight into the mechanisms that underlie their evolution. The Hox genes have been analyzed in insects, crustaceans and chelicerates. However, the expression patterns of the Hox genes have not yet been comprehensively analyzed in a myriapod. We present the expression patterns of the ten Hox genes in a centipede, Lithobius atkinsoni, and compare our results to those from studies in other arthropods. We have three major findings. First, we find that Hox gene expression is remarkably dynamic across the arthropods. The expression patterns of the Hox genes in the centipede are in many cases intermediate between those of the chelicerates and those of the insects and crustaceans, consistent with the proposed intermediate phylogenetic position of the Myriapoda. Second, we found two ‘extra’ Hox genes in the centipede compared with those in Drosophila. Based on its pattern of expression, Hox3 appears to have a typical Hox-like role in the centipede, suggesting that the novel functions of the Hox3 homologs zen and bicoid were adopted somewhere in the crustacean-insect clade. In the centipede, the expression of the gene fushi tarazu suggests that it has both a Hox-like role (as in the mite), as well as a role in segmentation (as in insects). This suggests that this dramatic change in function was achieved via a multifunctional intermediate, a condition maintained in the centipede. Last, we found that Hox expression correlates with tagmatic boundaries, consistent with the theory that changes in Hox genes had a major role in evolution of the arthropod body plan.

Mice doubly deficient for the Polycomb Group genes Mel18 and Bmi1 reveal synergy and requirement for maintenance but not initiation of Hox gene expression

Development ◽  
2001 ◽  
Vol 128 (9) ◽  
pp. 1587-1597 ◽  
Author(s):  
T. Akasaka ◽  
M. van Lohuizen ◽  
N. van der Lugt ◽  
Y. Mizutani-Koseki ◽  
M. Kanno ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Subsequent Development ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Gene Products ◽  
Hox Gene ◽  
Hox Cluster ◽  
Polycomb Group Genes ◽  
Mediate Cell

Polycomb group genes were identified as a conserved group of genes whose products are required in multimeric complexes to maintain spatially restricted expression of Hox cluster genes. Unlike in Drosophila, in mammals Polycomb group (PcG) genes are represented as highly related gene pairs, indicative of duplication during metazoan evolution. Mel18 and Bmi1 are mammalian homologs of Drosophila Posterior sex combs. Mice deficient for Mel18 or Bmi1 exhibit similar posterior transformations of the axial skeleton and display severe immune deficiency, suggesting that their gene products act on overlapping pathways/target genes. However unique phenotypes upon loss of either Mel18 or Bmi1 are also observed. We show using embryos doubly deficient for Mel18 and Bmi1 that Mel18 and Bmi1 act in synergy and in a dose-dependent and cell type-specific manner to repress Hox cluster genes and mediate cell survival of embryos during development. In addition, we demonstrate that Mel18 and Bmi1, although essential for maintenance of the appropriate expression domains of Hox cluster genes, are not required for the initial establishment of Hox gene expression. Furthermore, we show an unexpected requirement for Mel18 and Bmi1 gene products to maintain stable expression of Hox cluster genes in regions caudal to the prospective anterior expression boundaries during subsequent development.

Sign in / Sign up

Export Citation Format

Share Document