Targeting activity is required for SWI/SNF function in vivo and is accomplished through two partially redundant activator-interaction domains.

Mol Cell

Howard Hughes Medical Institute and Department of Biochemistry and Molecular Biology, 306 Althouse Laboratory, The Pennsylvania State University, University Park, PA 16802, USA.

Published: October 2003

The SWI/SNF complex is required for the expression of many yeast genes. Previous studies have implicated DNA binding transcription activators in targeting SWI/SNF to UASs and promoters. To determine how activators interact with the complex and to examine the importance of these interactions, relative to other potential targeting mechanisms, for SWI/SNF function, we sought to identify and mutate the activator-interaction domains in the complex. Here we show that the N-terminal domain of Snf5 and the second quarter of Swi1 are sites of activation domain contact. Deletion of both of these domains left the SWI/SNF complex intact but impaired its ability to bind activation domains. Importantly, while deletion of either domain alone had minor phenotypic effect, deletion of both resulted in strong SWI/SNF related phenotypes. Thus, two distinct activator-interaction domains play overlapping roles in the targeting activity of SWI/SNF, which is essential for its function in vivo.

Download full-text PDF

Source
http://dx.doi.org/10.1016/s1097-2765(03)00366-6DOI Listing

Publication Analysis

Top Keywords

activator-interaction domains
12
targeting activity
8
swi/snf function
8
function vivo
8
swi/snf complex
8
swi/snf
7
domains
5
targeting
4
activity required
4
required swi/snf
4

Similar Publications

Short amphipathic peptides are capable of binding to transcriptional coactivators, often targeting the same binding surfaces as native transcriptional activation domains. However, they do so with modest affinity and generally poor selectivity, limiting their utility as synthetic modulators. Here we show that incorporation of a medium-chain, branched fatty acid to the N-terminus of one such heptameric lipopeptidomimetic (LPPM-8) increases the affinity for the coactivator Med25 >20-fold (Ki >100 μM to 4 μM), rendering it an effective inhibitor of Med25 protein-protein interactions (PPIs).

View Article and Find Full Text PDF

In silico and in vitro assessment of androgen receptor antagonists.

Comput Biol Chem

June 2021

Biology, The Life Science Center, School of Science and Technology, Örebro University, SE-701 82, Örebro, Sweden. Electronic address:

There is a growing concern for male reproductive health as studies suggest that there is a sharp increase in prostate cancer and other fertility related problems. Apart from lifestyle, pollutants are also known to negatively affect the reproductive system. In addition to many other compounds that have been shown to alter androgen signaling, several environmental pollutants are known to disrupt androgen signaling via binding to androgen receptor (AR) or indirectly affecting the androgen synthesis.

View Article and Find Full Text PDF

Molecular mechanism of two nanobodies that inhibit PAI-1 activity reveals a modulation at distinct stages of the PAI-1/plasminogen activator interaction.

J Thromb Haemost

March 2020

Laboratory for Therapeutic and Diagnostic Antibodies, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.

Background: Plasminogen activator inhibitor-1 (PAI-1), a key inhibitor of plasminogen activators (PAs) tissue-type PA (tPA) and urokinase-type PA (uPA) plays a crucial role in many (patho)physiological processes (e.g., cardiovascular disease, tissue fibrosis) as well as in many age-related pathologies.

View Article and Find Full Text PDF
Article Synopsis
  • Eukaryotic transcription initiation relies on the interaction between transcriptional activators and the mediator complex, specifically the role of the p53 transcription factor with the MED25 subunit.
  • This study used NMR spectroscopy to analyze how the transactivation domain of p53 (p53TAD) interacts with the activator interaction domain (ACID) of MED25, revealing that the p53TAD2 sequence is crucial for this interaction.
  • The findings show that p53TAD2 binds to a hydrophobic groove in MED25 ACID, and this interaction mechanism is conserved across other transcriptional activators like ERM and VP16.
View Article and Find Full Text PDF

Transcriptional coactivators are a molecular recognition marvel because a single domain within these proteins, the activator binding domain or ABD, interacts with multiple compositionally diverse transcriptional activators. Also remarkable is the structural diversity among ABDs, which range from conformationally dynamic helical motifs to those with a stable core such as a β-barrel. A significant objective is to define conserved properties of ABDs that allow them to interact with disparate activator sequences.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!