| 2003 |
BAF60a (SMARCD1) directly interacts with the glucocorticoid receptor (GR) and with BRG1 and BAF155/BAF170, serving as a critical molecular bridge between nuclear receptors and the BRG1-containing SWI/SNF complex. BAF60a possesses at least two interaction surfaces: one for GR and BRG1, and a second for BAF155 and BAF170. A GR mutant (R488Q) that fails to interact with BAF60a in vitro showed reduced chromatin-remodeling and transcriptional activity. A BAF60a truncation mutant (BAF60a4-140) caused chromatin-specific loss of GR function and prevented GR interaction with the BRG1 complex. |
Co-immunoprecipitation, in vitro interaction assays, stable expression of dominant-negative truncation mutant, chromatin-based transcription assays, mutagenesis |
Molecular and cellular biology |
High |
12917342
|
| 2003 |
BAF60a interacts specifically with the VDR/RXR heterodimer complex (but not either individual receptor alone), both in liganded and unliganded states, and modulates transcriptional activity from both negative and enhancer VDREs. |
Modified yeast one-hybrid screen, pull-down assays, transient transfection/reporter assays, deletion analysis |
The Journal of steroid biochemistry and molecular biology |
Medium |
14698202
|
| 2008 |
BAF60a (SMARCD1) directly interacts with p53, specifically at the tetramerization domain of p53 via amino acids 108–150 of BAF60a, mediating recruitment of the SWI/SNF complex to p53 target gene promoters. siRNA knockdown of BAF60a or expression of the N-terminal BAF60a fragment uncoupled p53 from SWI/SNF and repressed p53-dependent apoptosis and cell cycle arrest. |
Yeast two-hybrid, Co-immunoprecipitation, episomal reporter (pREP4-luc), siRNA knockdown, deletion mapping |
The Journal of biological chemistry |
High |
18303029
|
| 2008 |
BAF60a (SMARCD1) is a molecular link between PGC-1alpha and the SWI/SNF chromatin-remodeling complex in hepatic lipid metabolism. PGC-1alpha mediates recruitment of BAF60a to PPARalpha-binding sites, leading to transcriptional activation of peroxisomal and mitochondrial fat-oxidation genes. Adenoviral overexpression of BAF60a in hepatocytes stimulated fatty acid beta-oxidation and ameliorated hepatic steatosis in vivo. |
Genome-wide coactivation assay, adenoviral overexpression in cultured hepatocytes and in vivo, chromatin immunoprecipitation, gene expression analysis |
Cell metabolism |
High |
18680712
|
| 2009 |
BAF60a (SMARCD1) directly interacts with the androgen receptor (AR) ligand-binding domain coactivator groove via an FxxFF motif in BAF60a in a hormone-dependent manner. BAF60a depletion by siRNA selectively blocked AR-driven TMPRSS2 expression in LNCaP cells while differentially affecting other AR target genes. |
FxxLF peptide motif screen, Co-immunoprecipitation with full-length proteins, site-directed mutagenesis of FxxFF motif, siRNA knockdown with endogenous gene expression readouts |
Molecular endocrinology (Baltimore, Md.) |
High |
19762545
|
| 2011 |
BAF60a acts as a coactivator of RORα in the liver, binding near ROR response elements (RORE) on Bmal1 and G6Pase promoters and remodeling chromatin to an active state. Liver-specific knockdown of BAF60a disrupted rhythmic expression of clock and metabolic genes and altered circulating metabolite profiles. |
Liver-specific knockdown (adenoviral shRNA), ChIP, gene expression profiling, serum-shock circadian assay in HepG2 cells |
Hepatology (Baltimore, Md.) |
High |
21725993
|
| 2014 |
Smarcd1 stimulates transcription of clock genes (notably Bmal1) through co-activation of RORα in vascular smooth muscle cells (VSMCs), and this co-activation is dependent on PGC-1α. Smarcd1 also inhibits VSMC proliferation and migration by blocking cell cycle re-entry and activating kinase signaling pathways. |
Gain- and loss-of-function in VSMCs, gene expression analysis, cell cycle and migration assays, co-activation reporter assays |
The Journal of pathology |
Medium |
24615205
|
| 2015 |
SMARCD1 depletion in embryonic stem cells (ESCs) altered chromatin and enhanced endodermal differentiation. ChIP-seq revealed SMARCD1 is both an activator and repressor enriched at developmental regulators, with its chromatin binding coinciding with H3K27me3. SMARCD1 knockdown caused H3K27me3 redistribution and increased H3K4me3 near TSS, including at the Klf4 locus, suggesting SMARCD1 restricts pluripotency by regulating H3K27 methylation. |
D-CAP (differential chromatin-associated proteins) biochemical assay, LC-MS/MS, ChIP-seq, gene expression analysis, shRNA knockdown |
Cell reports |
High |
25818293
|
| 2015 |
Hepatocyte-specific inactivation of Baf60a reduced bile acid production and cholesterol absorption, attenuating diet-induced hypercholesterolemia and atherosclerosis. Baf60a stimulates genes in bile acid synthesis, modification, and transport through a CAR/Baf60a feedforward regulatory loop and is required for SWI/SNF complex recruitment to enable an activating epigenetic switch on target genes. |
Hepatocyte-specific Baf60a conditional knockout mice, ChIP, gene expression analysis, metabolic measurements |
Cell reports |
High |
26586440
|
| 2015 |
miR-7 suppresses SMARCD1 protein expression by binding to two seed regions in the 3'UTR of SMARCD1 mRNA, and SMARCD1 knockdown interfered with the interaction between SMARCD1 and p53, reducing p53-dependent BAX and p21 expression, caspase-3 cleavage, and apoptosis upon chemotherapy treatment. |
Luciferase reporter assays with wild-type and mutated 3'UTR, Western blot, siRNA knockdown, cell viability and apoptosis assays |
The Journal of biological chemistry |
Medium |
26542803
|
| 2018 |
BAF60A mediates physical interaction between MITF and the BRG1-containing SWI/SNF complex during melanocyte differentiation. The interaction between MITF and BAF60A required the basic helix-loop-helix domain of MITF, and recombinant BAF60A directly pulled down recombinant MITF in the absence of other SWI/SNF subunits. BAF60A depletion inhibited melanin synthesis and MITF target gene expression; MITF promoted BAF60A recruitment to melanocyte-specific promoters, which was required for BRG1 recruitment and chromatin remodeling. |
Co-immunoprecipitation, recombinant protein pull-down, siRNA depletion, ChIP, gene expression analysis, melanin synthesis assay |
Journal of cellular physiology |
High |
30515787
|
| 2019 |
SMARCD1 mutations cause a syndromic neurodevelopmental disorder in humans. The Drosophila ortholog Bap60, knocked down in postmitotic mushroom body neurons of adult flies, caused defects in long-term memory and altered context-dependent expression of genes involved in neuron function and development during a critical window of juvenile adult brain development when synaptic connections are formed. |
Targeted Drosophila knockdown (UAS-RNAi), long-term memory behavioral assay, mushroom-body-specific transcriptome analysis, human clinical exome sequencing |
American journal of human genetics |
Medium |
30879640
|
| 2019 |
BAF60a represses hepatic ureagenesis by interacting with Y-box protein 1 (YB-1) to repress Cps1 transcription and switching the chromatin structure of the Cps1 promoter to an inhibitory state. PGC-1α and YB-1 competitively bind to BAF60a, selectively regulating fatty acid β-oxidation and ureagenesis in response to different nutrient states. |
Gain- and loss-of-function in mice (adenoviral overexpression, shRNA), ChIP, co-immunoprecipitation, gene expression analysis, serum ammonia measurements |
Molecular metabolism |
High |
32029232
|
| 2020 |
BAF60a regulates VSMC inflammation by recruiting BRG1 (the catalytic SWI/SNF subunit) to promoters of NF-κB target genes. VSMC-specific BAF60a knockout protected mice from Ang II- and elastase-induced AAA formation, suppressing vascular inflammation, monocyte infiltration, and elastin fragmentation. BAF60a also controls CTSS (cathepsin S) expression, preventing ECM degradation. |
VSMC-specific Baf60a knockout mice, RNA sequencing with pathway analysis, adenoviral overexpression in human aortic smooth muscle cells, siRNA knockdown, in vivo AAA models |
Arteriosclerosis, thrombosis, and vascular biology |
High |
32787523
|
| 2020 |
BAF60a maintains chromatin accessibility at PPARγ and EBF2 binding sites for key thermogenic genes in brown fat. Fat-specific BAF60a inactivation impaired cold-induced thermogenesis in brown fat but paradoxically triggered more pronounced cold-induced browning of inguinal white adipose tissue through induction of MC2R (a receptor for ACTH), revealing a dichotomous role of BAF60a-mediated chromatin remodeling in brown versus beige fat programs. |
Fat-specific Baf60a conditional knockout mice, ATAC-seq (chromatin accessibility), gene expression analysis, adrenergic/ACTH stimulation experiments |
Nature communications |
High |
32404872
|
| 2020 |
NMR spectroscopy revealed that both the N-terminal region and the SWIB domain of BAF60A directly interact with the tetramerization domain of p53. Specific residues Ile315, Met366, Ala388, and Tyr390 of BAF60A SWIB domain are involved in p53TET binding. The dissociation constant (KD) between BAF60ASWIB and p53TET is approximately 0.3 mM (weak affinity). |
NMR spectroscopy, pull-down analysis, KD measurement |
Biochemical and biophysical research communications |
High |
33168186
|
| 2021 |
Smarcd1 forms a transcription complex with the transcription factor Six2 in dopaminergic cells, binds to the 2840–2933 bp region of the GDNF promoter, and is required for Six2-mediated GDNF expression. Knockdown of Smarcd1 inhibited Six2's effect on GDNF transcription and increased apoptosis of 6-OHDA-injured DA neurons. |
LC-ESI-ITMS/MS (interactome screen), Co-immunoprecipitation, ChIP (promoter mapping), siRNA knockdown, overexpression, cell viability and apoptosis assays |
Neuroscience letters |
Medium |
34233203
|
| 2022 |
BAF60a inactivation in macrophages triggers proinflammatory gene expression through chromatin remodeling. The transcription factor Atf3 physically interacts with BAF60a to suppress proinflammatory gene expression. Myeloid-specific BAF60a KO promoted adipose tissue macrophage proinflammatory activation, exacerbating diet-induced obesity, insulin resistance, and metabolic dysfunction. |
Myeloid-specific Baf60a knockout mice, myeloid-specific overexpression, ATAC-seq, CUT&Tag-seq, transcriptome analysis, Co-IP (BAF60a–Atf3 interaction), in vivo metabolic phenotyping |
Diabetes |
High |
35822944
|
| 2023 |
BAF60a preserves mitochondrial energy homeostasis in macrophages under pro-atherogenic stimuli by retaining nuclear respiratory factor 1 (NRF1) accessibility at critical mitochondrial genes. Myeloid-specific Baf60a deletion compromised mitochondrial integrity in plaque macrophages, increasing adhesion, apoptosis, and plaque development. Overexpression of BAF60a rescued mitochondrial dysfunction in an NRF1-dependent manner. |
Myeloid-specific Baf60a knockout mice, adenoviral overexpression, chromatin accessibility analyses (NRF1 binding sites), mitochondrial function assays, in vivo atherosclerosis models |
Cell reports |
High |
37768825
|
| 2024 |
Smarcd1 is essential for lymphoid cell fate specification in murine hematopoiesis. Acute deletion of Smarcd1 caused lymphopenia with near-complete absence of early lymphoid progenitors and mature B and T cells, while myeloid and erythroid lineages were unaffected. Mechanistically, Smarcd1 interacts with the E2a transcription factor at proximal promoters and regulates distal enhancer activity to activate the lymphoid gene signature in multipotent progenitors. |
Conditional acute Smarcd1 deletion in adult murine hematopoiesis, flow cytometry, ChIP/ATAC, gene expression profiling, Co-IP (Smarcd1–E2a interaction) |
Developmental cell |
High |
39232562
|
| 2025 |
BAF60a physically interacts with Nkx6.1 in islet β cells to selectively modulate chromatin accessibility and transcriptional activity of genes critical for glucose-stimulated insulin secretion (GSIS). β cell-specific BAF60a inactivation impaired biphasic GSIS, causing hyperglycemia; restoration rescued β cell function. A human BAF60a V278M mutation that disrupts the BAF60a–Nkx6.1 interaction was identified and, when introduced into mice, caused β cell dysfunction and impaired glucose homeostasis. BAF60a deficiency also reduced GLP-1R and GIPR expression, attenuating the insulinotropic effect of GLP-1R agonists. |
β cell-specific Baf60a conditional knockout, adenoviral restoration, ATAC-seq, ChIP, Co-IP (BAF60a–Nkx6.1), human donor variant characterization, knock-in mouse model with V278M mutation, GSIS assays, in vivo glucose tolerance tests |
The Journal of clinical investigation |
High |
41052246
|
| 2025 |
PU.1 (SPI1) directly binds BAF60A within the BAF complex via a YEATS-like domain on BAF60A. A disordered region of PU.1 adopts a helical conformation upon binding to BAF60A. Disruption of the PU.1–BAF60A interface by knockdown abrogated PU.1's ability to rescue cell viability. Small molecules identified by high-throughput screening can disrupt the PU.1–BAF60A protein-protein interaction by binding to BAF60A at the critical interaction hotspot. |
Cryo-EM/structural biology, co-crystal structures of BAF60A with small molecules, co-IP, domain mapping, siRNA knockdown with functional cell viability assay, high-throughput screen |
bioRxivpreprint |
High |
|
| 2026 |
SMARCD1 directly binds the VEGFA promoter, enhances chromatin accessibility at the promoter, and modifies histone marks to activate VEGFA transcription in ccRCC cells. SMARCD1 knockdown reduced VEGFA expression and sensitized bevacizumab-resistant ccRCC models to anti-angiogenic therapy. |
ChIP-qPCR, ATAC-qPCR, luciferase reporter assays, siRNA knockdown, in vitro and in vivo tumor models |
BMC cancer |
Medium |
41872817
|
| 2026 |
The E3 ubiquitin ligase CHFR ubiquitinates SMARCD1 in Sertoli cells in response to palmitic acid (PA) exposure, leading to SMARCD1 degradation. Reduced SMARCD1 disrupts blood-testis barrier (BTB) integrity as evidenced by reduced ZO-1 and Cx43 expression. Smarcd1 haploinsufficient male mice showed compromised BTB integrity, and PA exposure further aggravated BTB disruption in these mice. |
E3 ligase identification (CHFR), ubiquitination assay, SMARCD1 protein stability analysis, Smarcd1+/- mouse model, cell viability assays, BTB marker expression analysis |
Chemico-biological interactions |
Medium |
41990863
|