Long-range repression in the Drosophila embryo.

Cai, Houjian; Arnosti, David N.; Levine, Michael

doi:10.1073/pnas.93.18.9309

Cited by 83 publications

(86 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Western blots demonstrating comparable expression levels of transfected Sbf1 and Sbf1 HCS as well as GAL4-SUV and GAL4-SUV ⌬C are shown as insets. (5,37). Consistent with this possible mechanism, SUV39H1 associates with M31 (HP1␤), the only other characterized mammalian su(var) homolog (1), and their cosedimentation supports participation in a su(var) complex distinct from two previously described mammalian PcG complexes (45,46).…”

Section: Discussionsupporting

confidence: 50%

“…4C). Therefore, SUV39H1 represses transcription when tethered to DNA, and its ability to do so appears promoter and distance independent consistent with chromatin-mediated silencing as opposed to promoter interference (5).…”

Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1mentioning

confidence: 99%

“…Notably, heterochromatin binding by the heterochromatin protein 1 [Su(var)2-5] is regulated by phosphorylation (57). Another dominant suppressor of variegation [Su(var) [3][4][5][6] is itself a type I protein phosphatase (3).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

View full text Add to dashboard Cite

Mammalian SET domain-containing proteins define a distinctive class of chromatin-associated factors that are targets for growth control signals and oncogenic activation. SUV39H1, a mammalian ortholog of Drosophila Su(var)3-9, contains both SET and chromo domains, signature motifs for proteins that contribute to epigenetic control of gene expression through effects on the regional organization of chromatin structure. In this report we demonstrate that SUV39H1 represses transcription in a transient transcriptional assay when tethered to DNA through the GAL4 DNA binding domain. Under these conditions, SUV39H1 displays features of a long-range repressor capable of acting over several kilobases to silence basal promoters. A possible role in chromatin-mediated gene silencing is supported by the localization of exogenously expressed SUV39H1 to nuclear bodies with morphologic features suggestive of heterochromatin in interphase cells. In addition, we show that SUV39H1 is phosphorylated specifically at the G 1 /S cell cycle transition and when forcibly expressed suppresses cell growth. Growth suppression as well as the ability of SUV39H1 to form nuclear bodies and silence transcription are antagonized by the oncogenic antiphosphatase Sbf1 that when hyperexpressed interacts with the SET domain and stabilizes the phosphorylated form of SUV39H1. These studies suggest a phosphorylation-dependent mechanism for regulating the chromatin organizing activity of a mammalian su(var) protein and implicate the SET domain as a gatekeeper motif that integrates upstream signaling pathways to epigenetic regulation and growth control.The formation and propagation of higher-order chromatin states are dynamic processes that establish distinct domains that are either permissive or restrictive for transcription. The functions of such domains have been implicated in the epigenetic control of developmental gene expression in Drosophila (38), proper sister chromatid segregation during meiosis (11), and telomeric and centromeric silencing in yeast (22,35). The molecular mechanisms that regulate these and other properties of higher-order chromatin are essentially unknown.Genetic analyses in Drosophila and yeast have identified several genes that participate in the formation of euchromatin or heterochromatin states. Some of these encode proteins that contribute to either an enhancement [E(var)] or suppression [Su(var)] of position effect variegation (PEV) (42). PEV is a gene silencing mechanism that results from the spreading of heterochromatin, thus implicating E(var) and Su(var) proteins in the formation of euchromatic and heterochromatic domains, respectively. Several E(var) and Su(var) proteins share distinctive motifs that are important for their ability to organize chromatin domains. The Su(var)3-9 protein and its mammalian ortholog SUV39H1 are unique in being the only characterized PEV modifiers that share two of these consensus motifs, the chromo and SET domains (1, 50). Chromo domains are 40-amino-acid modular motifs that are implicated in...

show abstract

Section: Discussionsupporting

confidence: 50%

Section: Sbf1 Physically Associates With the Set Domain Of Suv39h1mentioning

confidence: 99%

See 1 more Smart Citation

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Firestein

Cui

Huie

et al. 2000

Molecular and Cellular Biology

101

View full text Add to dashboard Cite

show abstract

“…The site-function analyses carried out on the endo16 and cyIIIa genes (20,21) have both revealed CRM target sites that are required in order for a function that is mediated by other sites elsewhere to have an effect at the level of BTA execution. In endo16, the spatial domain of the early phase of expression is confined to the future endoderm by repressors that bind at known target sites in upstream modules Ϸ1 kb away from module A, one of which is a cAMP-response element-binding protein factor.…”

Section: Examples Of Crm Logic Functions Controlling Directmentioning

confidence: 99%

Logic functions of the genomic cis-regulatory code

Istrail

Davidson

2005

Proc. Natl. Acad. Sci. U.S.A.

158

106

View full text Add to dashboard Cite

cis-regulatory modules that control developmental gene expression process the regulatory inputs provided by the transcription factors for which they contain specific target sites. A prominent class of cis-regulatory processing functions can be modeled as logic operations. Many of these are combinatorial because they are mediated by multiple sites, although others are unitary. In this work, we illustrate the repertoire of cis-regulatory logic operations, as an approach toward a functional interpretation of the genomic regulatory code.T he differential control of gene expression during development depends primarily on transcription factor interactions with cis-regulatory modules (CRMs) that may be located upstream, downstream, or in the introns of a gene. The potential regulatory functions encoded in the DNA sequence of these modular control units are specified by the combinations of transcription factor target sites they contain, and, typically, a CRM will include sites for four to eight different interactions (1, 2). In the last analysis, it may be said that we will understand the genomic regulatory code only when we can interpret its functional significance by inspection, because it has been possible for decades to recognize protein coding sequence. However, at present, we cannot even recognize many cis-regulatory target sites; nor, perhaps more importantly, can we specify predictively, or, in some cases, even properly name, the elemental functions mediated by the individual sites within a CRM. Here, we take a step toward analysis of the repertoire of elemental cis-regulatory functions.For a developmentally expressed gene, regulatory control always depends in part on transcription factors presented variably in embryonic time and space. In the following, we use the term "driver" for such factors. These drivers provide spatial and temporal inputs (positive and negative) reflected in the regulatory output of the relevant CRM and in the resulting pattern of gene expression. However, target sites for driver inputs (3) may often account for only a minority of specific CRM target sites. Furthermore, the regulatory outputs of a CRM never exactly equal any of its inputs. This finding can be perceived explicitly when the inputs and outputs are hooked together in a gene regulatory network (2, 4-6). Instead, the CRM processes the driver inputs in a variety of complex ways, depending on its genomic design and, to some extent, on its genomic environs. We find that there is a class of fundamental processing functions mediated by specific CRM target sites and combinations of sites that have the behavior of logic operations, and it is on these sites that we focus herein. Initial Insights from endo16Endo16 is a developmentally regulated gene of the sea urchin embryo expressed in endodermal territory. In respect to its genomic regulatory code, endo16 may be the best understood of any developmentally active gene. The functional significance of every detectable target site in the two key CRMs of this gene was determined by mutation...

show abstract

“…Several lines of evidence suggest that Brk is a versatile repressor, which can inhibit transcription by competing with activators for binding to a common site or by active repression. Active repressors can act either at short range, by inhibiting activity of activators bound to nearby elements (150 bp away or less), or at long range by interfering with activators bound at a greater distances (Cai et al, 1996). Brk can mediate active repression (Kirkpatrick et al, 2001), and binds the co-repressors dCtBP and Groucho (Gro), which mediate short-and long-range repression, respectively (Saller et al, 2002;Zhang et al, 2001).…”

Section: A Cre In the D-h Repression Element Is Required For Repressionmentioning

confidence: 99%

Opposing inputs by Hedgehog and Brinker define a stripe ofhairyexpression in theDrosophilaleg imaginal disc

et al. 2004

View full text Add to dashboard Cite

show abstract

Long-range repression in the Drosophila embryo.

Cited by 83 publications

References 29 publications

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Set Domain-Dependent Regulation of Transcriptional Silencing and Growth Control by SUV39H1, a Mammalian Ortholog of Drosophila Su(var)3-9

Logic functions of the genomic cis-regulatory code

Opposing inputs by Hedgehog and Brinker define a stripe ofhairyexpression in theDrosophilaleg imaginal disc

Contact Info

Product

Resources

About