| 2020 |
ESCO1 acetylates cohesinSTAG1 complexes, and together with CTCF protects a subset of cohesinSTAG1 from removal by WAPL, enabling formation of long and presumably long-lived chromatin loops. ESCO1 contributes to boundary formation in chromatin looping. |
Cell-based assays in mammalian G1-phase cells measuring cohesin chromatin residence time, CTCF and ESCO1 depletion experiments, chromatin fractionation, and loop boundary analysis |
eLife |
High |
32065581
|
| 2017 |
ESCO1 is responsible for the majority of SMC3 acetylation in vertebrate cells, but its acetyltransferase activity is largely dispensable for mitotic sister chromatid cohesion; instead, ESCO1-dependent SMC3 modification primarily regulates non-cohesive cohesin activities (DNA repair, transcriptional control, chromosome loop formation/stabilization). Cohesion establishment is critically dependent on ESCO2, mediated by sequences in ESCO2's N-terminus. |
ESCO1 and ESCO2 gene inactivation in vertebrate cells, sister chromatid cohesion assays, SMC3 acetylation measurements, domain-swap rescue experiments |
Proceedings of the National Academy of Sciences of the United States of America |
High |
28847955
|
| 2015 |
ESCO1 requires the cohesin regulatory subunit Pds5 (bound to Rad21) for SMC3 acetylation and sororin stabilization on chromatin. Pds5 interacts exclusively with ESCO1 (not ESCO2) via a unique and conserved N-terminal domain of ESCO1, and this interaction is essential for SMC3 acetylation and sister chromatid cohesion. ESCO1 localizes to cohesin sites on chromosomes throughout interphase in a Pds5-interaction-dependent manner and can acetylate SMC3 independently of DNA replication. |
Co-immunoprecipitation, Pds5 depletion experiments, chromosome localization assays (ChIP/immunofluorescence), domain mapping with ESCO1 mutants, cell-cycle-staged SMC3 acetylation assays |
Current biology : CB |
High |
26051894
|
| 2015 |
ESCO1 is recruited by cohesin to over 11,000 chromatin sites genome-wide throughout the cell cycle via two short N-terminal motifs (A-box and B-box) unique to ESCO1 orthologs. Deletion of either motif causes derepression of ESCO1-proximal genes and functionally uncouples cohesion from SMC3 acetylation. Distinct ESCO1 mutations can separate its roles in cohesion establishment versus gene silencing. |
ChIP-seq for ESCO1 and cohesin genome-wide, cell-cycle-staged chromatin recruitment, motif-deletion mutant analysis, gene expression assays (derepression), and sister chromatid cohesion assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
26305936
|
| 2016 |
X-ray crystal structure of the ESCO1 zinc finger–acetyltransferase domain reveals structural homology to the Gcn5 HAT but with unique additional features including a zinc finger and an ~40-residue loop region involved in protein stability and SMC3 substrate binding. Structure-based mutagenesis identified key residues for substrate binding and catalysis, and rationalized disease-associated mutation effects. |
X-ray crystallography, structure-based mutagenesis, biochemical acetyltransferase assays |
The Journal of biological chemistry |
High |
27803161
|
| 2016 |
Crystal structure of the ESCO1 acetyltransferase domain in complex with acetyl-CoA shows the active site lacks a canonical catalytic base. Mutation of surface glutamate E789 (near automodification target K803) strongly reduces ESCO1 autoacetylation. In vivo evidence (budding yeast Smc3 D114 mutant) indicates ESCO1 uses substrate-assisted catalysis for cohesion establishment. SAXS reveals ESCO1 is a dimer in solution. |
X-ray crystallography, SAXS, site-directed mutagenesis, in vivo yeast Smc3 acetylation assays |
Structure (London, England : 1993) |
High |
27112597
|
| 2018 |
In mouse oocyte meiosis, ESCO1 localizes to both nucleus and cytoplasm, binds α-tubulin, and is required for α-tubulin acetylation to maintain microtubule stability and proper spindle assembly. Enzymatically dead ESCO1-G768D cannot restore α-tubulin acetylation or rescue spindle defects, and purified wild-type (but not mutant) ESCO1 acetylates an α-tubulin peptide in vitro. |
siRNA depletion in mouse oocytes, co-immunoprecipitation (ESCO1–α-tubulin), overexpression rescue with wild-type vs. catalytic mutant ESCO1, nocodazole resistance assay, in vitro acetyltransferase assay with purified ESCO1 and α-tubulin peptide |
Nucleic acids research |
High |
29361031
|
| 2019 |
In porcine oocytes, ESCO1 localizes to the spindle apparatus (distinct from ESCO2, which is on chromosomes), binds α-tubulin, and is required for α-tubulin acetylation to maintain microtubule dynamics. Depletion of ESCO1 causes meiotic arrest with defective spindle/chromosome structure and reduced polar body extrusion. |
siRNA depletion in porcine oocytes, immunofluorescence localization, co-immunoprecipitation (ESCO1–α-tubulin), acetylated α-tubulin quantification |
Cell cycle (Georgetown, Tex.) |
Medium |
31387516
|
| 2017 |
In chicken DT40 cells, both ESCO1 and ESCO2 promote sister chromatid cohesion, but ESCO2 is additionally and specifically required for proliferation and centromere integrity. ESCO1 overexpression can fully suppress ESCO2-loss proliferation and centromere phenotypes but only partially rescues chromosome-arm cohesion defects. Combined inactivation of ESCO1 and ESCO2 causes lethality due to compromised mitotic chromosome segregation, and this lethality is not rescued by wapl deletion or acetyl-mimicking smc3-QQ mutations, indicating cohesion establishment is linked to interphase chromatin architecture. |
Conditional DT40 cell knockouts of ESCO1, ESCO2, WAPL, and SMC3 acetylation mutants; epistasis analysis; mitotic chromosome analysis; proliferation assays |
Genes & development |
High |
29196537
|
| 2020 |
In Warsaw Breakage Syndrome (WABS) cells lacking DDX11, residual sister chromatid cohesion (SCC) depends predominantly on ESCO2, not ESCO1. Reciprocally, Roberts Syndrome cells (lacking ESCO2) depend on DDX11 for residual SCC. Synthetic lethality between DDX11 and ESCO2 (but not ESCO1 and DDX11) is rescued by WAPL knockdown, placing ESCO1 and ESCO2 on different but related cohesin fractions. |
SCC assays in patient-derived cells, siRNA knockdowns, synthetic lethality analysis, mitotic delay quantification, WAPL rescue experiments, cDNA rescue with human/mouse constructs and DDX11 DNA-binding mutant |
PloS one |
Medium |
31935221
|
| 2023 |
The intrinsically disordered N-terminal tail of ESCO1 binds DNA with high affinity through electrostatic (charge-dependent) interactions. Neutralization of positive residues in the N-tail reduces DNA binding in vitro and reduces ESCO1 chromatin association in cells. Strikingly, disrupting DNA binding does not affect total SMC3 acetylation or sister chromatid cohesion, demonstrating that ESCO1 catalytic activity can occur independently of direct DNA binding. |
In vitro DNA-binding assays with purified ESCO1 N-tail, charge-neutralization mutagenesis, chromatin fractionation in cells, SMC3 acetylation assays, sister chromatid cohesion assays |
bioRxivpreprint |
Medium |
38106185
|