An Sp1/KLF binding site is important for the activity of a Polycomb group response element from the Drosophila engrailed gene

Brown, J. Lesley; Grau, Daniel J.; DeVido, Sarah K.; Kassis, Judith A.

doi:10.1093/nar/gki827

Cited by 76 publications

(80 citation statements)

References 57 publications

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“…We introduced a mutation that disrupts site A in PRE2 and assayed this mini-white reporter construct in transgenic flies for the ability to give PSS ( Figure 2D). When site A was mutated, PSS was reduced from 66% to 13% of the lines (comparable to what we see with mutation of either the Pho or the Spps sites) (Americo et al 2002;Brown et al 2005). We have identified the potential core-binding site of protein A to be GAACAG.…”

Section: Identification Of Site Asupporting

confidence: 86%

“…PREs act in transgenes to mediate the phenomenon of PSS of the mini-white gene (Kassis et al 1991;Kassis 1994Kassis , 2002. While there is some controversy as to whether all fragments of DNA that mediate PSS are PREs (Kassis 2002), in our studies of PREs from the en/inv region we have found a 100% correlation of fragments that demonstrate PRE activity in the maintenance assay and fragments that give PSS (Americo et al 2002;Brown et al 2005;Cunningham et al 2010). Here, we assay PSS of mini-white in transgenic lines carrying PREs with mutated binding sites to assess if a given binding site might play a role in PRE activity.…”

Section: Analysis Of Predicted Protein-binding Sites In En Presmentioning

confidence: 66%

“…PRE1, but not PRE2, was able to maintain the restricted expression of bxd-Ubx-lacZ in this chromosomal insertion site ( Figure 5A). That PRE2 did not maintain repression was somewhat surprising, since we previously showed that it was able to maintain the restricted pattern of the same bxd-Ubx-lacZ reporter gene at 9 of 12 chromosomal insertion sites in a P-element-based vector (Brown et al 2005). With RCME, constructs were inserted in the genome in either orientation, and similar results were obtained from both orientations.…”

Section: Pre1mentioning

confidence: 75%

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Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

Brown

Kassis

2013

Genetics

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Polycomb group response elements (PREs) play an essential role in gene regulation by the Polycomb group (PcG) repressor proteins in Drosophila. PREs are required for the recruitment and maintenance of repression by the PcG proteins. PREs are made up of binding sites for multiple DNA-binding proteins, but it is still unclear what combination(s) of binding sites is required for PRE activity.Here we compare the binding sites and activities of two closely linked yet separable PREs of the Drosophila engrailed (en) gene, PRE1 and PRE2. Both PRE1 and PRE2 contain binding sites for multiple PRE-DNA-binding proteins, but the number, arrangement, and spacing of the sites differs between the two PREs. These differences have functional consequences. Both PRE1 and PRE2 mediate pairing-sensitive silencing of mini-white, a functional assay for PcG repression; however, PRE1 requires two binding sites for Pleiohomeotic (Pho), whereas PRE2 requires only one Pho-binding site for this activity. Furthermore, for full pairing-sensitive silencing activity, PRE1 requires an AT-rich region not found in PRE2. These two PREs behave differently in a PRE embryonic and larval reporter construct inserted at an identical location in the genome. Our data illustrate the diversity of architecture and function of PREs.

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Section: Identification Of Site Asupporting

confidence: 86%

Section: Analysis Of Predicted Protein-binding Sites In En Presmentioning

confidence: 66%

Section: Pre1mentioning

confidence: 75%

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Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

Brown

Kassis

2013

Genetics

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“…The minimal essential binding site for KLF4 is 5Ј-G/AG/ AGGC/TGC/T-3Ј (33,34). There is a c-Myc binding site and two putative sequences similar to KLF4 binding sequences in the Bmi1 promoter (Fig.…”

Section: Klf4 Directly Binds Bmi1 Promoter and Regulates Bmi1 Expressmentioning

confidence: 99%

Regulation of the Potential Marker for Intestinal Cells, Bmi1, by β-Catenin and the Zinc Finger Protein KLF4

Chen

Zhang

et al. 2012

Journal of Biological Chemistry

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Background: Bmi1 is a potential marker for the intestinal stem cells. Results: Wnt regulates Bmi1 indirectly, while KLF4 directly inhibits Bmi1, as well as Bmi1-mediated histone ubiquitination in colon cancer cells. Conclusion: Bmi1 is required for colon cancer cell proliferation, and it is up-regulated in colon cancer tissues. Significance: Study of the mechanisms of Bmi1 regulation suggests potential targets for cancer therapeutics.

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“…However, earlier studies have demonstrated that Dsp1 can also act as a TrxG protein at other homeotic PRE/TREs (Decoville et al, 2001;Rappailles et al, 2005;Salvaing et al, 2006). Thus, although the synthetic PRE/TRE study has shown that Dsp1 is important for silencing at a specific minimal PRE/TRE fragment (Dejardin et al, 2005), it is not clear how this function may be modified by other features of this PRE/TRE that are present in its endogenous context, and how it may be different at other PRE/TREs.Clues to further pieces in the puzzle of PRE/TRE design come from two other recent studies, showing that the Grainy head (Grh) (Blastyak et al, 2006) and Sp1/KLF DNA-binding proteins (Brown et al, 2005) are each also vital for recruiting the PcG proteins to specific PRE/TREs. However, each of these reports studied only a single PRE/TRE, and colocalisation studies with known PcG or TrxG proteins on polytene chromosomes were not performed, making it difficult to assess whether these proteins are PRE/TREspecific regulators, or whether they play a more global role.…”

mentioning

confidence: 99%

Polycomb/Trithorax response elements and epigenetic memory of cell identity

2007

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DEVELOPMENT 223Polycomb/Trithorax group response elements (PRE/TREs) are fascinating chromosomal pieces. Just a few hundred base pairs long, these elements can remember and maintain the active or silent transcriptional state of their associated genes for many cell generations, long after the initial determining activators and repressors have disappeared. Recently, substantial progress has been made towards understanding the nuts and bolts of PRE/TRE function at the molecular level and in experimentally mapping PRE/TRE sites across whole genomes. Here we examine the insights, controversies and new questions that have been generated by this recent flood of data. IntroductionDuring the 1990s, studies of the regulation of homeotic genes in the Drosophila Bithorax complex (BX-C) uncovered very different behaviour for two classes of cis-regulatory DNA element: initiator elements and maintenance elements (or Polycomb/Trithorax group response elements, PRE/TREs) (Busturia et al., 1989;Chan et al., 1994;Chiang et al., 1995;Simon et al., 1993;Simon et al., 1990) (reviewed by Maeda and Karch, 2006). One can think of these two types of elements as 'shift workers' that use very different strategies to regulate the expression patterns of the same genes at different stages of embryonic development. In the first three hours of development, the initiator elements are in control: the output of each homeotic gene depends on the local concentrations of segmentation gene products (these are activators and repressors that are present in different concentrations at different positions of the embryo). However, a few hours after these homeotic gene patterns have been established, the segmentation gene products decay, and thus the positional information they provide is lost. The transcriptional history of each gene is subsequently maintained throughout the rest of development, and into adulthood, by the ubiquitously expressed Polycomb group (PcG) and Trithorax group proteins (TrxG), which work antagonistically via the PRE/TRE elements to maintain active (TrxG) or silenced (PcG) transcriptional states (Moehrle and Paro, 1994). Although the effects of mutations in the PcG and TrxG genes are seen only after the segmentation gene products decay, the PcG and TrxG proteins themselves appear to associate with PRE/TREs much earlier, so that PRE/TREs are 'preloaded' with PcG and TrxG proteins, ready to maintain the transcriptional states that are set by the transiently acting segmentation gene products (Orlando et al., 1998).The maintenance of transcriptional memory at PRE/TREs is 'epigenetic'. This term has suffered much overuse and abuse in recent years, but we use here the classical definition given by Ptashne and Gann (Ptashne and Gann, 2002) (p100): "a change in the state of expression of a gene that does not involve a mutation, but that is nevertheless inherited (after cell division) in the absence of the signal (or event) that initiated that change". In the case of PRE/TREs, the information required to turn gene activity off or on after ea...

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An Sp1/KLF binding site is important for the activity of a Polycomb group response element from the Drosophila engrailed gene

Cited by 76 publications

References 57 publications

Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

Architectural and Functional Diversity of Polycomb Group Response Elements in Drosophila

Regulation of the Potential Marker for Intestinal Cells, Bmi1, by β-Catenin and the Zinc Finger Protein KLF4

Polycomb/Trithorax response elements and epigenetic memory of cell identity

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