The developmental and pathogenic roles of BAF57, a special subunit of the BAF chromatin‐remodeling complex

Abstract

Edited by Claus AzzalinMammalian SWI/SNF or BAF chromatin-remodeling complexes are polymorphic assemblies of homologous subunit families that remodel nucleosomes. BAF57 is a subunit of the BAF complexes; it is encoded only in higher eukaryotes and is present in all mammalian assemblies. Its main structural feature is a high-mobility group domain, the DNA-binding properties of which suggest that BAF57 may play topological roles as the BAF complex enters or exits the nucleosome. BAF57 displays specific interactions with a number of proteins outside the BAF complex. Through these interactions, it can accomplish specific functions. In the embryo, BAF57 is responsible for the silencing of the CD4 gene during T-cell differentiation, and during the repression of neuronal genes in non-neuronal cells, BAF57 interacts with the transcriptional corepressor, Co-REST, and facilitates repression. Extensive work has demonstrated a specific role of BAF57 in regulating the interactions between BAF and nuclear hormone receptors. Despite its involvement in oncogenic pathways, new generation sequencing studies do not support a prominent role for BAF57 in the initiation of cancer. On the other hand, evidence has emerged to support a role for BAF57 as a metastasis factor, a prognosis marker and a therapeutic target. In humans, BAF57 is associated with disease, as mutations in this gene predispose to important congenital disorders, including menigioma disease or the Coffin-Siris syndrome. In this article, we present an exhaustive analysis of the BAF57 molecular and biochemical properties, cellular functions, loss-of-function phenotypes in living organisms and pathological manifestations in cases of human mutations.Keywords: Brg1/Brm-associated factors; cancer; chromatin remodeling; development; epigenetics; high-mobility group; inherited disorder; nuclear receptors The SWItch/sucrose nonfermentable (SWI/SNF) chromatin-remodeling complex facilitates the binding of transcriptional factors to nucleosomal templates through an ATP-dependent nucleosome disruption activity. First discovered in yeast, SWI/SNF was initially thought to have a transcription activating role

Differential expression of key subunits of SWI/SNF chromatin remodeling complexes in porcine embryos derived in vitro or in vivo

“…In murine embryonic stem cells, knockdown of BAF155 attenuated BAF57 and vice versa (Schaniel et al, ). BAF57 is found only in higher eukaryotes, and is a key subunit that facilitates interactions between SWI/SNF complexes and transcription factors (Lomelí & Castillo‐Robles, ). With the exception of some pronuclear embryos, BAF57 was detectable in most oocytes and embryos throughout preimplantation development—which is in accordance with reports that BAF57 is omnipresent in all mammalian assemblies (Lomelí & Castillo‐Robles, ).…”

smarce1 mutants have a defective endocardium and an increased expression of cardiac transcription factors in zebrafish

“…This activity is achieved by the Brahma (BRM/SMARCA2) or Brahma-Related Gene 1 (BRG1/SMARCA4) subunits. Three other subunits (BAF155/SMARCC1, BAF170/SMARCC2, BAF47/SMARCB1) together with BRG1 or BRM are sufficient to reconstitute a core complex capable of remodeling mononucleosomes in vitro 6 . Additionally, other subunits help to target the complex to specific genetic loci templates 1 , 7 , 8 .…”

BAFfling pathologies: Alterations of BAF complexes in cancer

“…Notably, the development of the disease occurs earlier in men (between 2 and 10 years of age) than in women (between 14 and 30 years of age). Although the underlying reason remains unknown, a hormonal role has been suggested in the growth of meningioma [132], consistent with the role of SMARCE1 in steroid hormone responses [47].…”