| 1996 |
Human ADA2 (hADA2/TADA2A) interacts with human GCN5 (hGCN5) in vivo as shown by yeast two-hybrid assay, and hGCN5 interacts with yeast ADA2, indicating conserved complex formation. hADA2 contains a cryptic activation domain, and GAL4-hADA2 activates transcription in HeLa cells; hADA2 or hGCN5 augments GAL4-VP16 activation. |
Yeast two-hybrid assay, transcriptional activation assays in yeast and HeLa cells |
Molecular and cellular biology |
Medium |
8552087
|
| 1997 |
The region of yeast ADA2 that interacts with yGCN5 maps to the amino terminus, which is highly conserved in hADA2/TADA2A, establishing structural conservation of the ADA2-GCN5 interaction interface. |
Yeast two-hybrid mapping with deletion constructs |
Molecular and cellular biology |
Medium |
8552087
|
| 1997 |
TADA2L (TADA2A) and GCN5L2 co-localize to chromosome 17q12-q21 and are expressed at relatively similar levels across all human tissues, suggesting coordinated regulation. |
Northern blot analysis, fluorescence in situ hybridization (FISH) |
Genomics |
Medium |
9073520
|
| 2000 |
hADA2/TADA2A is required for T3/GRIP1 and SRC-1 coactivator-dependent transcriptional activation by human thyroid hormone receptor (hTRbeta1) in yeast. hTRbeta1 binds directly to hADA2 in vitro protein-protein interaction experiments, placing TADA2A in the nuclear receptor coactivation pathway. |
Yeast genetics (ada mutants), in vitro protein-protein interaction, transcriptional reporter assays |
Molecular endocrinology |
Medium |
10809234
|
| 2005 |
Drosophila Ada2a null mutants are late-larval lethal and show defects in cell proliferation. Ada2a function is required in the female germ line. Ada2a null mutation does NOT reduce histone H3 K14 or H3 K9 acetylation (in contrast to Ada2b), establishing that ADA2a and ADA2b have distinct histone substrate specificities. |
Genetic null mutants, pole-cell transplantation germ-line mosaics, histone acetylation immunostaining |
Molecular and cellular biology |
High |
16135810
|
| 2005 |
The Drosophila Ada2a gene shares overlapping regulatory/promoter regions with the Dtl (PIMT) gene and also produces RPB4 via alternative splicing, establishing a complex genomic architecture for Ada2a. |
Reporter gene fusions in tissue culture and transgenic animals, alternative splicing analysis |
Gene |
Medium |
15777699
|
| 2005 |
TADA2A (TADA2L) shares a bidirectional promoter with ACACA in humans, mice, rats, and sheep; this shared promoter co-regulates transcripts for both genes in an asymmetric fashion, with RNA polymerase II concentration in the intergenic region reflecting transcript abundance differences. |
5'-RACE, RNA polymerase II ChIP, Northern analysis across tissues |
Genomics |
Medium |
15607423
|
| 2006 |
In Drosophila, loss of dAda2a results in reduced nucleosomal histone H4 acetylation at lysines 12 and 5, while H3 K9 and K14 acetylation (established by dAda2b-containing complexes) is unaffected. Genetic interaction between dGcn5 and dAda2a produces similar chromosome structural and developmental defects, placing dAda2a in an H4-specific GCN5-containing complex (ATAC). |
Genetic null mutants, immunostaining of polytene chromosomes, genetic interaction analysis |
Molecular and cellular biology |
High |
17030603
|
| 2007 |
In Drosophila, mutations in Ada2a (ATAC component) induce decondensation of the male X chromosome similar to NURF mutants. Ada2a chromosome binding and histone H4-Lys12 acetylation are compromised in Iswi and Nurf301 mutants, indicating that NURF nucleosome remodeling is required for ATAC/Ada2a to access chromatin. |
Genetic epistasis, polytene chromosome immunostaining, transcript profiling |
EMBO reports |
Medium |
18084186
|
| 2008 |
Human ATAC complex was purified and found to contain ADA2A (TADA2A), ADA3, GCN5 or PCAF, STAF36/WDR5, POLE3/CHRAC17, POLE4, TAK1/MAP3K7, MBIP, YEATS2, and NC2beta. The YEATS2-NC2beta histone fold module interacts with TBP and negatively regulates transcription when recruited to a promoter, establishing TADA2A as a core subunit of human ATAC distinct from STAGA. |
Biochemical purification (mass spectrometry), co-immunoprecipitation, transcriptional reporter assays |
The Journal of biological chemistry |
High |
18838386
|
| 2008 |
The Drosophila ATAC complex, containing Ada2a, is a double HAT complex with Gcn5 and Atac2 (KAT14) as two acetyltransferases. ATAC stimulates nucleosome sliding by ISWI, SWI-SNF, and RSC remodeling complexes but does not itself exhibit nucleosome-remodeling activity. |
MudPIT mass spectrometry, in vitro HAT assays with recombinant Atac2, in vitro nucleosome sliding assays |
Nature structural & molecular biology |
High |
18327268
|
| 2008 |
Mammalian ATAC complex contains GCN5, ATAC2, and ADA2A (TADA2A) among other subunits. ATAC2 depletion results in disassembly of the complex, showing that ATAC2 plays an architectural role in maintaining mammalian ATAC integrity—and consequently the functional complex containing TADA2A. |
Immunoprecipitation, RNAi depletion, in vitro HAT assay with recombinant ATAC2, Atac2 knockout mice |
Molecular and cellular biology |
High |
19103755
|
| 2010 |
ATAC complex (containing Ada2a/TADA2A) localizes to the mitotic spindle. RNAi depletion of Ada2a or Ada3 causes centrosome multiplication, defective spindle and midbody formation, binucleated cells, delayed M/G1 transition, and hyperacetylation of histone H4K16 and alpha-tubulin. ATAC/Gcn5-mediated acetylation targets Cyclin A for degradation, which regulates SIRT2 deacetylase activity, establishing a non-histone substrate role for ATAC in mitotic progression. |
RNAi knockdown, immunofluorescence localization, cell cycle FACS analysis, in vitro acetylation assays of Cyclin A/Cdk2 |
The EMBO journal |
High |
20562830
|
| 2015 |
The HAT module of human ATAC is composed of GCN5, ADA2a (TADA2A), ADA3, and SGF29. ADA2a-containing (ATAC) HAT module enhances GCN5 acetyltransferase activity, primarily acetylating histone H3K14. ADA2b (in SAGA) has a stronger influence on GCN5 activity than ADA2a. The lysine acetylation specificity of GCN5 on histone tails is not altered by incorporation into ATAC versus SAGA HAT modules. |
In vitro HAT assays with purified recombinant and endogenous HAT modules, histone tail peptides and full-length histones as substrates |
The Journal of biological chemistry |
High |
26468280
|
| 2017 |
Che-1/AATF interacts with ADA2A (TADA2A) and ADA2B in human cells (co-immunoprecipitation) and in yeast two-hybrid assays. Domain mapping identified the regions of ADA2A and GCN5 required for these interactions. |
Co-immunoprecipitation, co-localization, yeast two-hybrid domain mapping |
PloS one |
Medium |
29232376
|
| 2019 |
In Drosophila, Ada2a nucleates formation of the ATAC complex (distinct from SAGA which is nucleated by Ada2b). Only the Ada2b-PB isoform is in SAGA; Ada2b-PA forms the distinct CHAT complex. This establishes that Ada2a is the defining subunit of the ATAC complex. |
Affinity purification, mass spectrometry, genetic analysis of isoform-specific mutants |
Journal of cell science |
High |
30559249
|
| 2021 |
Alpha-synuclein A53T mutant preferentially localizes to the nucleus and binds TADA2A, identified as a novel binding partner via BioID proximity labeling. Alpha-synuclein A53T significantly reduces histone H3 acetylation in SH-SY5Y cells and in mouse striatum/substantia nigra after alpha-syn preformed fibril injection. TADA2A levels are decreased in the substantia nigra of Parkinson's disease patients, linking the alpha-syn A53T-TADA2A interaction to neurotoxicity. |
BioID proximity labeling, nuclear fractionation/localization, Western blot for histone H3 acetylation, mouse stereotaxic injection model, human PD tissue analysis |
International journal of molecular sciences |
Medium |
34065515
|
| 2021 |
TAZ-CAMTA1 and YAP-TFE3 oncogenic fusion proteins interact with YEATS2 and ZZZ3, components of the ATAC complex (which contains TADA2A/ADA2A), as identified by a combined proteomic/genetic screen. The fusion proteins drive a unique transcriptome by simultaneously hyperactivating TEAD-based transcription and modulating chromatin via interaction with ATAC. |
Proteomic screen (affinity purification/MS), genetic validation, integrative next-generation sequencing (ChIP-seq, RNA-seq) |
eLife |
Medium |
33913810
|
| 2022 |
In Drosophila, the histone acetyltransferase complex Ada2a-containing (ATAC) cooperates with Msl3 (H3K36me3 reader) and Set2 to regulate germline stem cell (GSC) differentiation during oogenesis, establishing a role for ATAC in GSC fate transition. |
Genetic mutant analysis, epistasis, transcriptional profiling in Drosophila oogenesis |
Development |
Medium |
34878097
|
| 2022 |
MSH6 stabilization in response to alkylation damage requires interactions with both MPTAC and the Ada2a-containing ATAC complex. MSH6 promotes sterol biosynthesis via the mevalonate pathway in a MPTAC- and ATAC-dependent manner, placing ATAC (and thus TADA2A) in an alkylation damage response-sterol biosynthesis pathway. |
Co-immunoprecipitation, RNAi knockdown, biochemical assays for sterol biosynthesis |
Redox biology |
Medium |
35189552
|