Polycomb group proteins and heritable silencing of Drosophila Hox genes

Development ◽  
2001 ◽  
Vol 128 (6) ◽  
pp. 993-1004 ◽  
Author(s):  
D. Beuchle ◽  
G. Struhl ◽  
J. Muller
Keyword(s):  
Transcriptional Repression ◽  
Hox Genes ◽  
Subsequent Development ◽  
Polycomb Group ◽  
Transcriptional Repressors ◽  
Proliferating Cells ◽  
Cis Acting ◽  
Drosophila Embryogenesis ◽  
Gap Genes ◽  
Polycomb Response Elements

Early in Drosophila embryogenesis, transcriptional repressors encoded by Gap genes prevent the expression of particular combinations of Hox genes in each segment. During subsequent development, those Hox genes that were initially repressed in each segment remain off in all the descendent cells, even though the Gap repressors are no longer present. This phenomenon of heritable silencing depends on proteins of the Polycomb Group (PcG) and on cis-acting Polycomb response elements (PREs) in the Hox gene loci. We have removed individual PcG proteins from proliferating cells and then resupplied these proteins after a few or several cell generations. We show that most PcG proteins are required throughout development: when these proteins are removed, Hox genes become derepressed. However, we find that resupply of at least some PcG proteins can cause re-repression of Hox genes, provided that it occurs within a few cell generations of the loss of repression. These results suggest a functional distinction between transcriptional repression and heritable silencing: in at least some contexts, Hox genes can retain the capacity to be heritably silenced, despite being transcribed and replicated. We propose that silenced Hox genes bear a heritable, molecular mark that targets them for transcriptional repression. Some PcG proteins may be required to define and propagate this mark; others may function to repress the transcription of Hox genes that bear the mark.

Regulation of proboscipedia in Drosophila by Homeotic Selector Genes

Genetics ◽  
2000 ◽  
Vol 156 (1) ◽  
pp. 183-194
Author(s):  
Douglas B Rusch ◽  
Thomas C Kaufman
Keyword(s):  
Expression Pattern ◽  
Regulatory Element ◽  
Polycomb Group ◽  
Accumulation Pattern ◽  
Cis Acting ◽  
Polycomb Group Genes ◽  
Gap Genes ◽  
Combined Action ◽  
Selector Genes

Abstract The gene proboscipedia (pb) is a member of the Antennapedia complex in Drosophila and is required for the proper specification of the adult mouthparts. In the embryo, pb expression serves no known function despite having an accumulation pattern in the mouthpart anlagen that is conserved across several insect orders. We have identified several of the genes necessary to generate this embryonic pattern of expression. These genes can be roughly split into three categories based on their time of action during development. First, prior to the expression of pb, the gap genes are required to specify the domains where pb may be expressed. Second, the initial expression pattern of pb is controlled by the combined action of the genes Deformed (Dfd), Sex combs reduced (Scr), cap'n'collar (cnc), and teashirt (tsh). Lastly, maintenance of this expression pattern later in development is dependent on the action of a subset of the Polycomb group genes. These interactions are mediated in part through a 500-bp regulatory element in the second intron of pb. We further show that Dfd protein binds in vitro to sequences found in this fragment. This is the first clear demonstration of autonomous positive cross-regulation of one Hox gene by another in Drosophila melanogaster and the binding of Dfd to a cis-acting regulatory element indicates that this control might be direct.

scholarly journals Defining the Boundaries of Polycomb Domains in Drosophila

Genetics ◽  
2020 ◽  
Vol 216 (3) ◽  
pp. 689-700
Author(s):  
Sandip De ◽  
Natalie D. Gehred ◽  
Miki Fujioka ◽  
Fountane W. Chan ◽  
James B. Jaynes ◽  
...  
Keyword(s):  
Target Genes ◽  
Additional Data ◽  
Transcription Unit ◽  
Polycomb Group ◽  
Transcriptional Repressors ◽  
Enhancer Activity ◽  
Transcriptional Terminator ◽  
Polycomb Repressive Complex 2 ◽  
Active Transcription ◽  
Polycomb Response Elements

Polycomb group (PcG) proteins are an important group of transcriptional repressors that act by modifying chromatin. PcG target genes are covered by the repressive chromatin mark H3K27me3. Polycomb repressive complex 2 (PRC2) is a multiprotein complex that is responsible for generating H3K27me3. In Drosophila, PRC2 is recruited by Polycomb Response Elements (PREs) and then trimethylates flanking nucleosomes, spreading the H3K27me3 mark over large regions of the genome, the “Polycomb domains.” What defines the boundary of a Polycomb domain? There is experimental evidence that insulators, PolII, and active transcription can all form the boundaries of Polycomb domains. Here we divide the boundaries of larval Polycomb domains into six different categories. In one category, genes are transcribed toward the Polycomb domain, where active transcription is thought to stop the spreading of H3K27me3. In agreement with this, we show that introducing a transcriptional terminator into such a transcription unit causes an extension of the Polycomb domain. Additional data suggest that active transcription of a boundary gene may restrict the range of enhancer activity of a Polycomb-regulated gene.

Involvement of the Polycomb-group geneRing1Bin the specification of the anterior-posterior axis in mice

Development ◽  
2002 ◽  
Vol 129 (18) ◽  
pp. 4171-4183 ◽  
Author(s):  
Maki Suzuki ◽  
Yoko Mizutani-Koseki ◽  
Yu-ichi Fujimura ◽  
Hiro Miyagishima ◽  
Tomomi Kaneko ◽  
...  
Keyword(s):  
Transcriptional Repression ◽  
Hox Genes ◽  
Protein Complexes ◽  
Mouse Genome Informatics ◽  
Axial Skeleton ◽  
Polycomb Group ◽  
Polycomb Group Protein ◽  
Chromosomal Dna ◽  
Polycomb Group Genes ◽  
Group Protein

The products of the Polycomb group of genes form complexes that maintain the state of transcriptional repression of several genes with relevance to development and in cell proliferation. We have identified Ring1B, the product of the Ring1B gene (Rnf2 – Mouse Genome Informatics), by means of its interaction with the Polycomb group protein Mel18. We describe biochemical and genetic studies directed to understand the biological role of Ring1B. Immunoprecipitation studies indicate that Ring1B form part of protein complexes containing the products of other Polycomb group genes, such as Rae28/Mph1 and M33, and that this complexes associate to chromosomal DNA. We have generated a mouse line bearing a hypomorphic Ring1B allele, which shows posterior homeotic transformations of the axial skeleton and a mild derepression of some Hox genes (Hoxb4, Hoxb6 and Hoxb8) in cells anterior to their normal boundaries of expression in the mesodermal compartment. By contrast, the overexpression of Ring1B in chick embryos results in the repression of Hoxb9 expression in the neural tube. These results, together with the genetic interactions observed in compound Ring1B/Mel18 mutant mice, are consistent with a role for Ring1B in the regulation of Hox gene expression by Polycomb group complexes.

scholarly journals Distinct p63 and p73 Protein Interactions Predict Specific Functions in mRNA Splicing and Polyploidy Control in Epithelia

Cells ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 25
Author(s):  
Julian M. Rozenberg ◽  
Olga S. Rogovaya ◽  
Gerry Melino ◽  
Nickolai A. Barlev ◽  
Alexander Kagansky
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Genome Stability ◽  
Spindle Assembly Checkpoint ◽  
Genotoxic Stress ◽  
Protein Protein Interactions ◽  
Proliferating Cells ◽  
P53 Family ◽  
Differentiated Cells ◽  
Specific Localization

Epithelial organs are the first barrier against microorganisms and genotoxic stress, in which the p53 family members p63 and p73 have both overlapping and distinct functions. Intriguingly, p73 displays a very specific localization to basal epithelial cells in human tissues, while p63 is expressed in both basal and differentiated cells. Here, we analyse systematically the literature describing p63 and p73 protein–protein interactions to reveal distinct functions underlying the aforementioned distribution. We have found that p73 and p63 cooperate in the genome stability surveillance in proliferating cells; p73 specific interactors contribute to the transcriptional repression, anaphase promoting complex and spindle assembly checkpoint, whereas p63 specific interactors play roles in the regulation of mRNA processing and splicing in both proliferating and differentiated cells. Our analysis reveals the diversification of the RNA and DNA specific functions within the p53 family.

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 The cis-Acting Family of Repeats Can Inhibit as well as Stimulate Establishment of an oriPReplicon

2001 ◽  
Vol 75 (22) ◽  
pp. 10709-10720 ◽  
Author(s):  
Elizabeth R. Leight ◽  
Bill Sugden
Keyword(s):  
Inhibitory Activity ◽  
Binding Sites ◽  
Replication Fork ◽  
Epigenetic Modification ◽  
Cell Generation ◽  
Dna Looping ◽  
Proliferating Cells ◽  
Cis Acting ◽  
The Family ◽  
Dyad Symmetry

ABSTRACT Previously we have shown that the establishment of anoriP replicon is dependent on its epigenetic modification, which occurs in only 1 to 10% of proliferating cells (E. R. Leight and B. Sugden, Mol. Cell. Biol. 21:4149–4161, 2001). To gain insights into the cis-acting requirements for the establishment of oriP replicons, we monitored the replication of oriP plasmid derivatives for several weeks following their introduction into cells. In EBNA-1-positive 143B and H1299 cells, plasmids containing only the region of dyad symmetry (DS) of oriP replicated but were lost more rapidly from cells than were oriP plasmids, demonstrating that the family of repeats (FR) of oriP acts in cis to stimulate replication in these cells. Unexpectedly, we found that the DS plasmid was established efficiently in 293/EBNA-1 cells, being lost at a rate of only 8% per cell generation over 24 days posttransfection. However, plasmids containing the FR in addition to the DS of oriPreplicated but were lost at a rate of approximately 30% per cell generation in 293/EBNA-1 cells, indicating that the FR inhibitsoriP's establishment in this cell line. FR's enhancement of transcription of a promoter in cis and FR's ability to inhibit replication fork movement do not account solely fororiP's inefficient establishment. In addition, DNA looping between FR and DS neither stimulates nor inhibits replication. Deletion of 11 EBNA-1 binding sites in the FR or replacement of the FR with DS sequences, however, does overcome the inhibitory activity of the FR, thereby allowing efficient establishment of the oriPderivative in 293/EBNA-1 cells.

scholarly journals Short germ insects utilize both the ancestral and derived mode of Polycomb group-mediated epigenetic silencing of Hox genes

Biology Open ◽  
2015 ◽  
Vol 4 (6) ◽  
pp. 702-709 ◽  
Author(s):  
Y. Matsuoka ◽  
T. Bando ◽  
T. Watanabe ◽  
Y. Ishimaru ◽  
S. Noji ◽  
...  
Keyword(s):  
Hox Genes ◽  
Polycomb Group ◽  
Epigenetic Silencing

scholarly journals Transcriptional repression by Drosophila and mammalian Polycomb group proteins in transfected mammalian cells.

1994 ◽  
Vol 14 (3) ◽  
pp. 1721-1732 ◽  
Author(s):  
C A Bunker ◽  
R E Kingston
Keyword(s):  
Binding Sites ◽  
Transcriptional Repression ◽  
Fusion Proteins ◽  
Mammalian Cells ◽  
Polycomb Group ◽  
Polycomb Group Proteins ◽  
Related Gene ◽  
Activation Domains ◽  
Sex Combs ◽  
Significant Homology

The Polycomb group (Pc-G) genes are essential for maintaining the proper spatially restricted expression pattern of the homeotic loci during Drosophila development. The Pc-G proteins appear to function at target loci to maintain a state of transcriptional repression. The murine oncogene bmi-1 has significant homology to the Pc-G gene Posterior sex combs (Psc) and a highly related gene, Suppressor two of zeste [Su(z)2]. We show here that the proteins encoded by bmi-1 and the Pc-G genes Polycomb (Pc) and Psc as well as Su(z)2 mediate repression in mammalian cells when targeted to a promoter by LexA in a cotransfection system. These fusion proteins repress activator function by as much as 30-fold, and the effect on different activation domains is distinct for each Pc-G protein. Repression is observed when the LexA fusion proteins are bound directly adjacent to activator binding sites and also when bound 1,700 bases from the promoter. These data demonstrate that the products of the Pc-G genes can significantly repress activator function on transiently introduced DNA. We suggest that this function contributes to the stable repression of targeted loci during development.

scholarly journals A lineage-specific requirement for YY1 Polycomb Group protein function in early T cell development

Development ◽  
2021 ◽  
Vol 148 (7) ◽  
Author(s):  
Anna L. F. V. Assumpção ◽  
Guoping Fu ◽  
Deependra K. Singh ◽  
Zhanping Lu ◽  
Ashley M. Kuehnl ◽  
...  
Keyword(s):  
T Cell ◽  
Protein Function ◽  
Transcriptional Repression ◽  
T Cell Development ◽  
Cell Development ◽  
Polycomb Group ◽  
Conditional Knockout ◽  
Specific Requirement ◽  
Polycomb Group Protein ◽  
Group Protein

ABSTRACT Yin Yang 1 (YY1) is a ubiquitous transcription factor and mammalian Polycomb Group protein (PcG) with important functions for regulating lymphocyte development and stem cell self-renewal. YY1 mediates stable PcG-dependent transcriptional repression via recruitment of PcG proteins that result in histone modifications. Many questions remain unanswered regarding how cell- and tissue-specificity is achieved by PcG proteins. Here, we demonstrate that a conditional knockout of Yy1 in the hematopoietic system results in an early T cell developmental blockage at the double negative (DN) 1 stage with reduced Notch1 signaling. There is a lineage-specific requirement for YY1 PcG function. YY1 PcG domain is required for T and B cell development but not necessary for myeloid cells. YY1 functions in early T cell development are multicomponent and involve both PcG-dependent and -independent regulations. Although YY1 promotes early T cell survival through its PcG function, its function to promote the DN1-to-DN2 transition and Notch1 expression and signaling is independent of its PcG function. Our results reveal how a ubiquitously expressed PcG protein mediates lineage-specific and context-specific functions to control early T cell development.

A silencer is required for maintenance of transcriptional repression throughout Drosophila development

Development ◽  
1997 ◽  
Vol 124 (21) ◽  
pp. 4343-4350 ◽  
Author(s):  
A. Busturia ◽  
C.D. Wightman ◽  
S. Sakonju
Keyword(s):  
Protein Interactions ◽  
Transcriptional Repression ◽  
Transcriptional Silencing ◽  
Active Role ◽  
Polycomb Group ◽  
Homeotic Genes ◽  
Protein Protein Interactions ◽  
Drosophila Development ◽  
Larval Stages ◽  
Associated Proteins

Transcriptional silencing by the Polycomb Group of genes maintains the position-specific repression of homeotic genes throughout Drosophila development. The Polycomb Group of genes characterized to date encode chromatin-associated proteins that have been suggested to form heterochromatin-like structures. By studying the expression of reporter genes, we have identified a 725 bp fragment, called MCP725, in the homeotic gene Abdominal-B, that accurately maintains position-specific silencing during proliferation of imaginal cells. Silencing by MCP725 requires the Polycomb and the Polycomblike genes, indicating that it contains a Polycomb response element To investigate the mechanisms of transcriptional silencing by MCP725, we have studied its temporal requirements by removing MCP725 from the transgene at various times during development. We have discovered that excision of MCP725 during larval stages leads to loss of silencing. Our findings indicate that the silencer is required for the maintenance of the repressed state throughout cell proliferation. They also suggest that propagation of the silenced state does not occur merely by templating of a heterochromatin structure by virtue of protein-protein interactions. Rather, they suggest that silencers play an active role in the maintenance of the position-specific repression throughout development.

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