corepressor complex to repress transcription in vivo
01 Jan 2003-
About: The article was published on 2003-01-01 and is currently open access. It has received 3 citations till now. The article focuses on the topics: Corepressor & Transcription (biology).
Citations
More filters
TL;DR: Interestingly, when CD20-negative cells were treated with 5-aza-2'-deoxycytidine in vitro, the expression of CD20 mRNA was stimulated within 3 days, resulting in the restoration of both cell surface expression of the CD20 protein and rituximab sensitivity, suggesting that some epigenetic mechanisms may be partly related to the down-regulation ofCD20 expression after ritUXimab treatment.
222 citations
TL;DR: It is shown that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3, and for the first time provides complementary gain‐ and loss‐of functional evidence in vivo for a cofactor, Dot 1L, in gene activationby TR during vertebrate development.
Abstract: Histone modifications are associated with transcriptional regulation by diverse transcription factors. Genome-wide correlation studies have revealed that histone activation marks and repression marks are associated with activated and repressed gene expression, respectively. Among the histone activation marks is histone H3 K79 methylation, which is carried out by only a single methyltransferase, disruptor of telomeric silencing-1-like (DOT1L). We have been studying thyroid hormone (T3)-dependent amphibian metamorphosis in two highly related species, the pseudo-tetraploid Xenopus laevis and diploid Xenopus tropicalis, as a model for postembryonic development, a period around birth in mammals that is difficult to study. We previously showed that H3K79 methylation levels are induced at T3 target genes during natural and T3-induced metamorphosis and that Dot1L is itself a T3 target gene. These suggest that T3 induces Dot1L expression, and Dot1L in turn functions as a T3 receptor (TR) coactivator to promote vertebrate development. We show here that in cotransfection studies or in the reconstituted frog oocyte in vivo transcription system, overexpression of Dot1L enhances gene activation by TR in the presence of T3. Furthermore, making use of the ability to carry out transgenesis in X. laevis and gene knockdown in X. tropicalis, we demonstrate that endogenous Dot1L is critical for T3-induced activation of endogenous TR target genes while transgenic Dot1L enhances endogenous TR function in premetamorphic tadpoles in the presence of T3. Our studies thus for the first time provide complementary gain- and loss-of functional evidence in vivo for a cofactor, Dot1L, in gene activation by TR during vertebrate development.-Wen, L., Fu, L., Shi, Y.-B. Histone methyltransferase Dot1L is a coactivator for thyroid hormone receptor during Xenopus development.
12 citations
Cites methods from "corepressor complex to repress tran..."
...Chromatin immunoprecipitation (ChIP) assay on oocyte samples was done essentially as previously described (37, 62, 63)....
[...]
TL;DR: It is shown that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3, and different isoforms of E 1A have distinct effects on TR function.
Abstract: The human adenovirus type 5 early region 1A (E1A) is one of two oncogenes present in the adenovirus genome and functions by interfering with the activities of cellular regulatory proteins. The E1A gene is alternatively spliced to yield five products. Earlier studies have revealed that E1A can regulate the function of thyroid hormone (T3) receptors (TRs). However, analysis in yeast compared with transfection studies in mammalian cell cultures yields surprisingly different effects. Here, we have examined the effect of E1A on TR function by using the frog oocyte in vivo system, where the effects of E1A can be studied in the context of chromatin. We demonstrate that different isoforms of E1A have distinct effects on TR function. The two longest forms inhibit both the repression by unliganded TR and activation by T3-bound TR. We further show that E1A binds to unliganded TR to displace the endogenous corepressor nuclear receptor corepressor, thus relieving the repression by unliganded TR. On the other hand, in the presence of T3, E1A inhibits gene activation by T3-bound TR indirectly, through a mechanism that requires its binding domain for the general coactivator p300. Taken together, our results thus indicate that E1A affects TR function through distinct mechanisms that are dependent upon the presence or absence of T3.
9 citations
References
More filters
Book•
01 Jan 2002
TL;DR: This "Factsbook" is devoted to nuclear receptors and describes the mode of action of the receptors in general and contains detailed entries covering each type of receptor.
Abstract: "The FactsBook Series" has established itself as the best source of easily accessible and accurate facts about protein groups. They use an easy-to-follow format and are researched and compiled by experts in the field. This "Factsbook" is devoted to nuclear receptors. The first section presents an introduction and describes the mode of action of the receptors in general. The second section of the book contains detailed entries covering each type of receptor. Entries provide information on: Nomenclature and structure; Isolation; DNA binding properties; Ligands; Expression; Target genes; Knockouts; Disease association; Gene structure, promoter and isoforms; Chromosomal location; Amino acid sequences; and Key references.
263 citations