Preferred Label : hSWI-SNF Pathway;
NCIt related terms : Chromatin Remodeling by hSWI/SNF ATP-dependent Complexes;
Alternative definition : BIOCARTA: The eukaryotic genome is packaged by histone and nonhistone proteins to
form chromatin. The assembly of nucleosomes, as well as compaction of nucleosomal
arrays into higher-order chromatin structures, creates a highly restrictive environment
for nuclear processes that require access to DNA. The packaging of eukaryotic DNA
into nucleosomes inhibits the access of factors to DNA and thus results in the repression
of transcription, replication, and recombination. To counterbalance the repressive
nature of chromatin, a variety of chromatin remodeling factors use the energy of ATP
hydrolysis to facilitate the interaction of proteins with nucleosomal DNA. ATP dependent
chromatin remodeling complexes are characterized by the presence of an ATPase subunit
from the SNF2-like family of the DEAD/H (SF2) DNA-stimulated ATPases. The highly conservative
hSWI/SNF multisubunit complexes contain hBRM or BRG1 ATPases which alter the histone-DNA
contacts enabling the access of general transcription factors to promoter regions.
Remodeling complexes are targeted to promoters via interactions with sequence-specific
transcription factors. Since chromatin constitutes a barrier for processes affecting
DNA, such a transcription, replication, and repair, a mechanism is required that can
open up or remodel chromatin to make it accessible to replication and transcription
factors. Steroid receptors are a class of transcription factors that can interact
with the repressive chromatin structure and remodel the chromatin to allow other transcription
factors to bind. In addition to nuclear receptors, transcription activators as divergent
as erythroid Kruppel-like factor, C/EBPs, c-Myc, MyoD, HSF1, and EBNA2 have also been
found to recruit SWI/SNF to specific promoters. The role of steroid receptors in chromatin
remodeling and transcription is exemplified by the glucocorticoid receptor (GR)-mediated
transactivation of the mouse mammary tumor virus (MMTV) promoter. The MMTV promoter
is organized into a phased array of six nucleosomes when stably integrated into mammalian
cells. The second nucleosome (nucB) is positioned over the binding sites for the GR
and nuclear factor 1 (NF1). Binding of NF1 is essential for GR-mediated transactivation
of the MMTV promoter; in the absence of glucocorticoid, the chromatin structure of
the promoter excludes the binding of NF1. Upon hormone administration, GR recruits
an ATP-dependent remodeling hSWI/SNF complex (BRG1-BAF) to remodel the chromatin Individually,
the GR makes direct interactions with BRG1-associated factor 60a (BAF60a) and BAF57.
Further, BAF60a possesses at least two interaction surfaces, one for GR and BRG1 and
a second for BAF155 and BAF170.The remodeling process converts the closed conformation
of the MMTV promoter to an open one without altering the nucleosomal positioning.
The remodeling of the promoter permits NF1 binding and the assembly of a transcription
initiation complex. (This definition may be outdated - see the DesignNote.);
NCIt note : The BIOCARTA Definition (ALT_DEFINITION) for this pathway concept was provided by
BioCarta. This property was not created by, nor is it maintained by the NCI Thesaurus
staff. Additionally, BioCarta is no longer updating its pathway data; thus, the BIOCARTA
Definition might be outdated or inaccurate. Please see the Terms and Conditions for
Use at http://www.biocarta.com/.;
Biocarta ID : h_hSWI-SNFpathway;
Origin ID : C39109;
UMLS CUI : C1515646;
Semantic type(s)
- has_gene_product_element
- pathway_has_gene_element
