scholarly journals Definition of the transcription factor TdIF1 consensus-binding sequence through genomewide mapping of its binding sites

2015 ◽  
Vol 20 (3) ◽  
pp. 242-254 ◽  
Author(s):  
Kotaro Koiwai ◽  
Takashi Kubota ◽  
Nobuhisa Watanabe ◽  
Katsutoshi Hori ◽  
Osamu Koiwai ◽  
...  
2020 ◽  
Author(s):  
Lothar Hennighausen ◽  
Hye Kyung Lee

SummaryGenetic variants associated with diseases are enriched in genomic sequences linked to regulatory regions, such as enhancers, super-enhancers and possibly repressors, that control nearby and distant genes. A known allergic and autoimmune risk locus at chromosome 11q13.51,2 is associated with the LRRC32 gene, which encodes GARP, a protein critical for TGF-β delivery3. This region coincides with a candidate enhancer that was predicted by the presence of activating chromatin marks and contains a polymorphism significantly associated with GARP expression on CD4+CD127-CD25+ Treg cells4. In the mouse, binding of the cytokine-induced transcription factor STAT5 was detected at two sites within the expansive candidate enhancer region and a 2.3 kb deletion resulted in reduced Lrrc32 expression4. However, a clear definition of the enhancer units controlled by STAT5 and a functional understanding of STAT5 in the regulation of Lrrc32 are needed. Here we use high-resolution ChIP-seq and identify three STAT5 binding sites within the Lrrc32 super-enhancer, one shared between Treg cells and mammary epithelium and one specific to each respective cell type. Using mice that express only 10% of normal STAT5 levels we demonstrate the defining contribution of STAT5 in the activation of the Lrrc32 super-enhancer.


2006 ◽  
Vol 26 (16) ◽  
pp. 5983-5993 ◽  
Author(s):  
Timothy J. Parnell ◽  
Emily J. Kuhn ◽  
Brian L. Gilmore ◽  
Cecilia Helou ◽  
Marc S. Wold ◽  
...  

ABSTRACT Eukaryotic genomes are divided into independent transcriptional domains by DNA elements known as insulators. The gypsy insulator, a 350-bp element isolated from the Drosophila gypsy retrovirus, contains twelve degenerate binding sites for the Suppressor of Hairy-wing [Su(Hw)] protein. Su(Hw) associates with over 500 non-gypsy genomic sites, the functions of which are largely unknown. Using a bioinformatics approach, we identified 37 putative Su(Hw) insulators (pSIs) that represent regions containing clustered matches to the gypsy insulator Su(Hw) consensus binding sequence. The majority of these pSIs contain fewer than four Su(Hw) binding sites, with only seven showing in vivo Su(Hw) association, as demonstrated by chromatin immunoprecipitation. To understand the properties of the pSIs, these elements were tested for enhancer-blocking capabilities using a transgene assay system. In a complementary set of experiments, effects of the pSIs on transcriptional regulation of genes at the natural genomic location were determined. Our data suggest that pSIs have complex genomic functions and, in some cases, establish insulators. These studies provide the first direct evidence that the Su(Hw) protein contributes to the regulation of gene expression in the Drosophila genome through the establishment of endogenous insulators.


Author(s):  
Arnav Moudgil ◽  
Daofeng Li ◽  
Silas Hsu ◽  
Deepak Purushotham ◽  
Ting Wang ◽  
...  

Abstract Summary Transposon calling cards is a genomic assay for identifying transcription factor binding sites in both bulk and single cell experiments. Here, we describe the qBED format, an open, text-based standard for encoding and analyzing calling card data. In parallel, we introduce the qBED track on the WashU Epigenome Browser, a novel visualization that enables researchers to inspect calling card data in their genomic context. Finally, through examples, we demonstrate that qBED files can be used to visualize non-calling card datasets, such as Combined Annotation-Dependent Depletion scores and GWAS/eQTL hits, and thus may have broad utility to the genomics community. Availability and implementation The qBED track is available on the WashU Epigenome Browser (http://epigenomegateway.wustl.edu/browser), beginning with version 46. Source code for the WashU Epigenome Browser with qBED support is available on GitHub (http://github.com/arnavm/eg-react and http://github.com/lidaof/eg-react). A complete definition of the qBED format is available as part of the WashU Epigenome Browser documentation (https://eg.readthedocs.io/en/latest/tracks.html#qbed-track). We have also released a tutorial on how to upload qBED data to the browser (http://dx.doi.org/10.17504/protocols.io.bca8ishw).


1971 ◽  
Vol 68 (1_Suppl) ◽  
pp. S223-S246 ◽  
Author(s):  
C. R. Wira ◽  
H. Rochefort ◽  
E. E. Baulieu

ABSTRACT The definition of a RECEPTOR* in terms of a receptive site, an executive site and a coupling mechanism, is followed by a general consideration of four binding criteria, which include hormone specificity, tissue specificity, high affinity and saturation, essential for distinguishing between specific and nonspecific binding. Experimental approaches are proposed for choosing an experimental system (either organized or soluble) and detecting the presence of protein binding sites. Techniques are then presented for evaluating the specific protein binding sites (receptors) in terms of the four criteria. This is followed by a brief consideration of how receptors may be located in cells and characterized when extracted. Finally various examples of oestrogen, androgen, progestagen, glucocorticoid and mineralocorticoid binding to their respective target tissues are presented, to illustrate how researchers have identified specific corticoid and mineralocorticoid binding in their respective target tissue receptors.


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