| 2005 |
The chromodomain of yeast Chd1 specifically interacts with methylated lysine 4 on histone H3 (H3K4me) and is a component of the SAGA and SLIK HAT complexes; SLIK shows enhanced acetylation of a methylated substrate dependent on a functional methyl-binding chromodomain, both in vitro and in vivo. |
Co-immunoprecipitation, in vitro binding assays, histone acetyltransferase assays with methylated substrates |
Nature |
High |
15647753
|
| 2005 |
Human CHD1 (but not yeast Chd1) directly and selectively binds histone H3 methylated at lysine 4 (H3K4me2/3) via its tandem chromodomains acting cooperatively, with Kd ~5 µM for di- and trimethyl H3K4. |
In vitro binding studies, dissociation constant measurements, domain mutagenesis |
The Journal of biological chemistry |
High |
16263726
|
| 2005 |
CHD1 functions as an ATP-dependent chromatin assembly factor, existing predominantly as a monomer; it catalyzes processive transfer of histones from the NAP1 chaperone to DNA, yielding regularly spaced nucleosomes with a shorter repeat length than ACF, and cannot assemble chromatin containing histone H1. |
Purified reconstitution assay with CHD1, NAP1, core histones, and relaxed DNA; comparative analysis with ACF |
Nature structural & molecular biology |
High |
15643425
|
| 2003 |
Yeast Chd1 interacts with transcription elongation factors Rtf1 (Paf1 complex), Spt4-Spt5, and Spt16-Pob3 (FACT), co-immunoprecipitates with these elongation factors, and associates with actively transcribed chromatin regions; deletion of CHD1 suppresses cold-sensitive spt5 mutations. |
Two-hybrid screen, co-immunoprecipitation, genetic suppression, chromatin immunoprecipitation |
The EMBO journal |
High |
12682017
|
| 2007 |
CHD1 is required for deposition of histone variant H3.3 into the male pronucleus in Drosophila embryos; CHD1 interacts with histone chaperone HIRA in cytoplasmic extracts, and its elimination abolishes H3.3 incorporation and leads to failure of paternal genome participation in zygotic mitosis. |
Genetic knockout in Drosophila, immunofluorescence, co-immunoprecipitation with HIRA |
Science (New York, N.Y.) |
High |
17717186
|
| 2010 |
The double chromodomain unit of Chd1 blocks DNA binding and activation of the ATPase motor in the absence of nucleosome substrates; an acidic helix joining the chromodomains packs against a DNA-binding surface of the ATPase motor; disruption of the chromodomain-ATPase interface prevents discrimination between nucleosomes and naked DNA and reduces reliance on histone H4 tail for nucleosome sliding. |
Crystal structure of Chd1, site-directed mutagenesis, ATPase and nucleosome sliding assays |
Molecular cell |
High |
20832723
|
| 2011 |
The DNA-binding domain of Chd1 contains SANT and SLIDE domains required for nucleosome binding and remodeling; site-directed mutagenesis of key residues reduces DNA binding and nucleosome sliding activity; homologous SLIDE domains were identified in CHD6-9 proteins. |
Crystal structure determination, site-directed mutagenesis, nucleosome binding and remodeling assays |
The EMBO journal |
High |
21623345
|
| 2011 |
The DNA-binding domain of Chd1 is critical for centering mononucleosomes on short DNA fragments by sensing extranucleosomal DNA; replacing the native DNA-binding domain with foreign DNA-binding domains (AraC or engrailed) redirects nucleosome sliding toward their respective target DNA sequences, demonstrating that the DNA-binding domain's affinity for extranucleosomal DNA dictates sliding direction. |
Domain-swap experiments, nucleosome sliding assays with foreign DNA-binding domains fused to Chd1 |
Molecular and cellular biology |
High |
21969605
|
| 2012 |
Chd1 (along with Isw1b) prevents trans-histone exchange over coding regions of actively transcribed genes; Isw1b is recruited to open reading frames via H3K36 methylation through the PWWP domain of Ioc4, and acts in conjunction with Chd1 to maintain chromatin integrity during transcription elongation. |
Genome-wide histone exchange assays, in vitro binding assays, genetic deletion analyses in S. cerevisiae |
Nature structural & molecular biology |
High |
22922743
|
| 2017 |
Cryo-EM structure of Chd1 bound to a nucleosome at 4.8 Å reveals that Chd1 detaches two turns of DNA from the histone octamer; SANT and SLIDE domains contact detached DNA at SHL -7; ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the histone H4 N-terminal tail; the double chromodomain swings toward nucleosomal DNA at SHL +1 causing ATPase closure. |
Cryo-electron microscopy structure determination, comparison with transition state-mimicking compounds |
Nature |
High |
29019976
|
| 2018 |
Cryo-EM structures of yeast Chd1 engaged with nucleosomes in ADP-beryllium fluoride transition state show contacts conserved with single-strand translocases plus additional contacts with both strands unique to Snf2-related proteins; Chd1 binding prises two turns of linker DNA off the histone octamer and re-orients both the histone H3 tail and ubiquitin conjugated to H2B K120 toward the unraveled DNA. |
Cryo-EM structure determination with transition state mimic ADP-beryllium fluoride |
eLife |
High |
30079888
|
| 2021 |
Cryo-EM structures show that Pol II transcription through a nucleosome is facilitated by Chd1 and FACT when elongation factors Spt4/5 and TFIIS are present; Pol II transcription exposes the proximal H2A-H2B dimer, releasing the inhibitory DNA-binding region of Chd1 to pump DNA toward Pol II; subsequently, FACT binds the partially unraveled nucleosome and excludes Chd1 and Spt5. |
Cryo-EM structural analysis of transcribing Pol II-Spt4/5-nucleosome complexes with Chd1 or FACT; in vitro transcription biochemistry |
Nature structural & molecular biology |
High |
33846633
|
| 2009 |
Chd1 is required to maintain the open/euchromatic chromatin of pluripotent mouse embryonic stem cells; it associates with promoters of active genes, and its downregulation leads to heterochromatin accumulation and loss of pluripotency; Chd1 is also required for efficient somatic cell reprogramming. |
RNAi knockdown in mouse ESCs, chromatin immunoprecipitation, differentiation assays, reprogramming assays |
Nature |
High |
19587682
|
| 2009 |
CHD1 interacts with SSRP1 (a subunit of FACT) both in vivo and in vitro; CHD1 associates with centromeres in a SSRP1-dependent manner; CHD1 knockdown reduces CENP-A deposition at centromeres; the CENP-H complex facilitates CENP-A deposition cooperatively with FACT and CHD1. |
Conditional mutant cell lines, co-immunoprecipitation, RNAi knockdown, immunofluorescence at centromeres |
Molecular biology of the cell |
High |
19625449
|
| 1995 |
CHD1 preferentially binds to A.T-rich tracts in double-stranded DNA via minor-groove interactions; DNA-binding activity maps to a 229-amino-acid C-terminal segment; CHD1 is a bulk chromatin constituent extractable with high salt or EDTA after micrococcal nuclease digestion; CHD1 is released into the cytoplasm during mitosis and reincorporated during telophase-cytokinesis. |
DNA binding assays, nuclear fractionation, immunocytochemistry, subcellular localization during cell cycle |
Molecular and cellular biology |
High |
7739555
|
| 1999 |
Both the chromodomain and ATPase/helicase-like domain of CHD1 are essential for proper chromatin association; CHD1 interacts in vivo with SSRP1 (an HMG box protein/FACT subunit) via an N-terminal segment outside the chromodomain; CHD1 and SSRP1 co-localize in mammalian nuclei and on Drosophila polytene chromosomes. |
Transient transfection with mutant CHD1, co-immunoprecipitation, immunocytochemistry |
Chromosoma |
High |
10199952
|
| 2011 |
Murine Chd1 is recruited to naive chromatin and more so to H3K4me3 chromatin; the Mediator coactivator complex is required for CHD1 recruitment; CHD1 associates with PIC components including Mediator; coimmunoprecipitation of CHD1 and Mediator is abolished by shRNA knockdown of a specific Mediator subunit. |
MuDPIT mass spectrometry of purified PICs, co-immunoprecipitation, shRNA knockdown, genome-wide ChIP |
Genes & development |
High |
21979373
|
| 2016 |
CHD1 reads the dimethylated K114 mark on KDM1A (LSD1); CHD1 is identified as a KDM1A K114me2 reader, and the co-crystal structure of the KDM1A K114me2-CHD1 chromodomain interaction is determined; genome-wide analyses show chromatin co-localization of KDM1A K114me2, CHD1, and androgen receptor (AR) in prostate tumor cells; this assembly drives AR-dependent transcription and TMPRSS2-ERG gene fusions. |
Co-crystal structure, genome-wide ChIP-seq, co-immunoprecipitation, functional transcription and translocation assays |
Nature structural & molecular biology |
High |
26751641
|
| 2017 |
PTEN stimulates GSK3β-mediated phosphorylation of CHD1 degron domains, promoting CHD1 degradation via β-TrCP-mediated ubiquitination-proteasome pathway; PTEN deficiency stabilizes CHD1, which then engages H3K4me3 to activate the TNF-NF-κB pro-tumorigenic gene network. |
Phosphorylation assays, ubiquitination assays, proteasome inhibition, genetic PTEN manipulation, transcriptome analyses |
Nature |
High |
28166537
|
| 2014 |
Chd1 is recruited to promoter-proximal nucleosomes of actively transcribed genes and is responsible for the vast majority of Pol II-directed nucleosome turnover; dominant-negative Chd1 increases Pol II stalling past the entry site of promoter-proximal nucleosomes; Chd1 evicts nucleosomes downstream of the promoter to enable Pol II promoter escape. |
MNase-ChIP with dominant-negative Chd1, nucleosome turnover assays, Pol II distribution mapping |
eLife |
High |
24737864
|
| 2016 |
Chd1 shifts hexasomes unidirectionally because it requires H2A/H2B on the entry side for sliding; ubiquitin-conjugated H2B on the entry side of asymmetric nucleosomes stimulates nucleosome sliding by Chd1. |
Nucleosome sliding assays with defined hexasomes and asymmetric nucleosomes, Widom 601 positioning sequence |
eLife |
High |
28032848
|
| 2017 |
Site-specific cross-linking shows Chd1 chromodomains and ATPase motor bind adjacent SHL1 and SHL2 sites on nucleosomal DNA and pack against the DNA-binding domain on DNA exiting the nucleosome, bridging both DNA gyres and ~90-bp nucleosomal loop; this architecture enables Chd1 to sense extranucleosomal DNA and provides a basis for nucleosome spacing and directional sliding. |
Site-specific cross-linking, structural biochemistry, functional sliding assays |
Molecular cell |
High |
28111016
|
| 2017 |
Monomeric Chd1 shifts nucleosomal DNA bidirectionally by dynamically alternating between different segments of the nucleosome; it generates unstable remodeling intermediates that relax to pre-remodeled positions; the DNA-binding domain and chromodomains are key regulatory domains controlling substrate discrimination and direction of sliding. |
Single-molecule FRET imaging, ATPase assays, domain truncation analysis |
Molecular cell |
High |
28943314
|
| 2013 |
CHD1 is required for efficient recruitment of AR to responsive promoters; CHD1 inactivation in vitro prevents formation of ERG rearrangements by impairing AR-dependent transcription; CHD1 regulates expression of AR-responsive tumor suppressors NKX3-1, FOXO1, and PPARγ. |
RNAi in vitro knockdown, ChIP for AR recruitment, FISH for ERG rearrangements, gene expression analysis |
Cancer research |
High |
23492366
|
| 2016 |
CHD1 is required for CtIP recruitment to chromatin and end resection during DNA double-strand break repair; CHD1 loss specifically affects HR-mediated DNA repair but not NHEJ; CHD1 depletion sensitizes cells to PARP inhibitors. |
ChIP for CtIP, DNA repair assays (HR vs. NHEJ), PARP inhibitor sensitivity assays in prostate cancer cells |
EMBO reports |
High |
27596623
|
| 2017 |
CHD1 loss leads to decreased error-free HR repair and increased error-prone NHEJ repair; CHD1 regulates 53BP1 stability; CHD1 loss sensitizes cells to DNA damaging therapy with evidence from in vitro, in vivo, and patient-derived organoid cultures. |
Genetically engineered mouse model, isogenic cell lines, patient-derived organoids, HR/NHEJ repair assays, 53BP1 stability analysis |
Annals of oncology |
High |
28383660
|
| 2018 |
CHD1 loss in human cells reduces γH2AX formation at DSBs due to both global reduction in H2AX incorporation and poor retention of H2AX at DSBs, and impairs CtIP recruitment; an N-terminal region of CHD1 negatively regulates DNA binding, ATPase, chromatin assembly and remodeling activities. |
CHD1 CRISPR knockout, chromatin immunoprecipitation at single DSB, H2AX incorporation analysis, domain deletion experiments |
Nucleic acids research |
High |
29529298
|
| 2017 |
CHD1 promotes XPC-to-TFIIH handover during global genome nucleotide excision repair (GG-NER) of UV lesions in nucleosomal DNA; CHD1 is recruited to UV lesions in a XPC-dependent manner; CHD1 depletion slows CPD excision and sensitizes cells to UV-induced cytotoxicity. |
Chromatin immunoprecipitation of chromatin fragments, chromatin fractionation, immunofluorescence for NER factors, UV sensitivity assays, siRNA knockdown |
The EMBO journal |
High |
29018037
|
| 2019 |
CHD1 occupies prostate-specific enhancers enriched for AR and lineage-specific cofactors; upon CHD1 loss, the AR cistrome is redistributed to an oncogenic pattern driving tumor formation; this cistrome shift activates a unique AR transcriptional signature enriched for pro-oncogenic pathways. |
ChIP-seq for CHD1 and AR, ATAC-seq, mouse prostate tumor model, RNA-seq |
Cancer cell |
High |
30930119
|
| 2022 |
Cryo-EM structure of Chd1 bound to a nucleosome in a nucleotide-free state at 2.3 Å shows the remodeler stimulates the nucleosome to absorb an additional nucleotide on each strand: on the tracking strand within the ATPase binding site (with local A-form geometry transformation) and on the guide strand one helical turn away; a histone-binding motif (ChEx) is identified that can block opposing remodelers and may allow Chd1 to participate in histone reorganization during transcription. |
Cryo-EM structure determination at 2.3 Å resolution |
Nature structural & molecular biology |
High |
35173352
|
| 2012 |
Chd1 is required for maintenance of high levels of H2B monoubiquitination (H2BK123ub) but not for H3K4 and H3K79 trimethylation; loss of Chd1 reduces nucleosomal occupancy in gene bodies; Chd1's function in maintaining H2BK123ub is conserved from yeast to humans. |
Genome-wide ChIP-seq, genetic deletion, H2B ubiquitination assays in yeast and human cells |
Genes & development |
High |
22549955
|
| 2003 |
CHD1 co-immunoprecipitates with histone deacetylase (HDAC) activity and associates with the transcriptional corepressor NCoR in yeast two-hybrid and in vitro pull-down assays; CHD1 also interacts with splicing proteins mKIAA0164, Srp20, and SAF-B; CHD1 overexpression affects alternative splicing. |
Co-immunoprecipitation, yeast two-hybrid, in vitro pull-down, splicing assays |
Biochemical and biophysical research communications |
Medium |
12890497
|
| 2021 |
Chd1 interacts with several DNA repair factors including ATM, PARP1, KAP1, and Topoisomerase 2β; absence of Chd1 leads to accumulation of DNA double-strand breaks at Chd1-bound Pol II-transcribed genes and rDNA in ES cells; genes prone to DSBs in Chd1 KO are longer genes with GC-rich promoters and labile nucleosomal structure. |
Co-immunoprecipitation, γH2AX ChIP-seq, CRISPR knockout, nascent transcription assays |
Nature communications |
High |
34381042
|
| 2021 |
FACT is recruited to the +1 nucleosome as it is partially unwrapped by engaging RNAPII and then spreads to downstream nucleosomes aided by Chd1; single-molecule tracking and genome-wide mapping demonstrate Chd1-dependent FACT spreading. |
High-resolution genome-wide mapping, single-molecule tracking, mathematical modeling, genetic deletion |
Molecular cell |
High |
34380014
|
| 2021 |
Autoinhibitory elements of Chd1 (chromodomains and bridge) reinforce each other to block nucleosome sliding by preventing initiation of twist defects; they target nucleotide-free and ADP-bound states of the ATPase motor to favor a partially disengaged state when the DNA-binding domain is not bound to entry-side DNA. |
Nucleotide-state specific functional assays, domain mutant sliding assays, ATPase coupling measurements |
Proceedings of the National Academy of Sciences of the United States of America |
High |
33468676
|
| 2018 |
The Chd1 ATPase motor stimulates DNA unwrapping from the edge of the nucleosome in a nucleotide-dependent and DNA sequence-sensitive fashion; with AMP-PNP, DNA primarily unwraps in-plane with the nucleosomal disk; with ADP·BeF3-, significant out-of-plane unwrapping occurs; unwrapping does not require the Chd1 DNA-binding domain. |
Stopped-flow binding kinetics, bulk FRET, small-angle X-ray scattering (SAXS) with contrast variation |
Nucleic acids research |
High |
29850894
|
| 2024 |
Cryo-EM structures of Chd1 bound to hexasome-nucleosome complexes show Chd1 positions its ATPase domain to shift the hexasome away from the nucleosome; in the absence of inner H2A/H2B dimer, the DNA-binding domain packs against the ATPase domain suggesting an inhibited state; restoration of the inner dimer by FACT triggers DBD displacement and stimulates Chd1 remodeling. |
Cryo-EM structure determination of Chd1-hexasome-nucleosome complexes, in vitro reconstitution |
Molecular cell |
High |
39270644
|
| 2011 |
Crystal structure of the S. cerevisiae Chd1 DNA-binding domain in complex with DNA reveals the SLIDE domain contacts the DNA major groove (unlike predicted minor-groove binding); contacts with the phosphate backbone occur primarily on one DNA strand; DNA lays across Chd1 at a distinct angle compared to ISW1a. |
X-ray crystal structure determination of Chd1 DNA-binding domain-DNA complex |
The Journal of biological chemistry |
High |
22033927
|
| 2017 |
Chd1 remodeler is sensitive to the sequence of nucleosomal DNA; poly(dA:dT) tracts within one and a half helical turns of SHL2 perturb remodeling without blocking ATPase engagement at SHL2, but instead promote multiple translational positions of DNA with respect to both Chd1 and the histone core; this sequence sensitivity is independent of the DNA-binding domain. |
Kinetic and equilibrium sliding assays, site-specific cross-linking, domain mutant analysis |
Journal of molecular biology |
High |
28189426
|
| 2020 |
CHD1 loss results in global changes in open and closed chromatin (ATAC-seq) with transcriptomic changes; integrative CRISPR-based functional screening identified four transcription factors (NR3C1, POU3F2, NR2F1, TBX2) that contribute to antiandrogen resistance through non-luminal lineage programs when CHD1 is lost. |
shRNA screen in vivo, ATAC-seq, RNA-seq, CRISPR functional screening |
Cancer cell |
High |
32220301
|
| 2020 |
CHD1 activates IL6 transcription in PTEN-deficient prostate cancer; CHD1 deletion reduces MDSC recruitment to the tumor microenvironment and increases CD8+ T cells; IL6 is identified as a key transcriptional target of CHD1 mediating MDSC recruitment. |
Conditional genetic knockout in mouse models (Pten/Smad4 GEMMs), tumor microenvironment analysis, transcriptional target identification |
Cancer discovery |
High |
32385075
|
| 2014 |
Chd1 is required for transcriptional output of both Pol I (ribosomal RNA) and Pol II in the mouse epiblast; Chd1 directly binds ribosomal DNA; Chd1-deficient ESCs show genome-wide reduction in transcriptional output correlating with lower RNAPII engagement with transcribed genes. |
Knockout mouse embryos, ChIP for Pol II, nascent transcript analysis, rDNA binding assays, nucleolar morphology |
Development (Cambridge, England) |
High |
25480920
|
| 2016 |
CHD1 interacts with the influenza virus polymerase complex; CHD1 recognizes H3K4me3 and downregulation of CHD1 reduces viral polymerase activity, viral RNA transcription, and production of infectious particles; CHD1 and RNAPII are co-degraded during influenza infection. |
Co-immunoprecipitation of CHD1 with viral polymerase, RNAi knockdown, viral polymerase activity assay, viral RNA quantification |
Journal of virology |
Medium |
26792750
|
| 2011 |
In S. pombe, Chd1 remodelers (Hrp1 and Hrp3) are responsible for nucleosome spacing activity in vitro and together are essential for aligning regular nucleosomal arrays over gene coding regions linked to transcription start sites in vivo; deletion of Hrp1 and/or Hrp3 leads to increased cryptic antisense transcription. |
In vitro nucleosome spacing assays with purified proteins, genome-wide nucleosome sequencing, cryptic transcription assays |
The EMBO journal |
High |
23103765
|
| 2019 |
Chd1 deletion in yeast leads to defects in sister chromatid cohesion and chromosome morphology; Chd1 acts as a regulator of cohesin with effects on Pds5 expression levels; in human prostate cancer, CHD1 expression correlates with cohesin gene expression. |
Genetic deletion, sister chromatid cohesion assays, chromosome morphology analysis, gene expression analysis |
Scientific reports |
Medium |
31222142
|
| 2017 |
CHD1 loss results in increased RNAPII pausing and decreased H2A.Z occupancy close to the TSS of differentiation-activated genes during osteoblast differentiation; CHD1 occupancy increases around the TSS of differentiation-activated genes and is required for their induction. |
ChIP-seq for CHD1, RNAPII, H2A.Z; RNA-seq; siRNA knockdown; in vivo ectopic bone formation |
Nucleic acids research |
High |
28475736
|
| 2021 |
CHD1 controls H3.3 incorporation in adult Drosophila brain; Chd1 disruption reduces H3.3 levels in fly heads as quantified by mass spectrometry; Chd1 and H3.3 chaperone HIRA show strong genetic interaction; loss of CHD1 leads to global de-repression of transcription, altered metabolism, and shortened lifespan. |
Quantitative mass spectrometry for histone variants, genetic interaction analysis, brain-specific rescue experiments |
Cell reports |
High |
34610319
|