SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 is a protein that in humans is encoded by the SMARCD3 gene. [5] [6] [7]
SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily D member 3 is a protein that in humans is encoded by the SMARCD3 gene. [5] [6] [7]
The protein encoded by this gene is a member of the SWI/SNF family of proteins, whose members display helicase and ATPase activities and which are thought to regulate transcription of certain genes by altering the chromatin structure around those genes. The encoded protein is part of the large ATP-dependent chromatin remodeling complex SNF/SWI and has sequence similarity to the yeast Swp73 protein.
Multiple alternatively spliced transcript variants have been found for this gene. [7] Mutually exclusive incorporation of the variants into the larger SWI/SNF complex are thought to direct the complex to remodel particular sites in chromatin, leading to alterations in gene activity that dictate cell behavior or differentiation during development and disease. [8]
SMARCD3 together with TBX15 triggers development glycolytic fast-twitch muscles by the activation of the Akt/PKB signaling pathway. [9]
In molecular biology, SWI/SNF, is a subfamily of ATP-dependent chromatin remodeling complexes, which is found in eukaryotes. In other words, it is a group of proteins that associate to remodel the way DNA is packaged. This complex is composed of several proteins – products of the SWI and SNF genes, as well as other polypeptides. It possesses a DNA-stimulated ATPase activity that can destabilize histone-DNA interactions in reconstituted nucleosomes in an ATP-dependent manner, though the exact nature of this structural change is unknown. The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, enabling binding of specific transcription factors, and allowing genes to be activated or repressed.
Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.
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