| 2005 |
The chromodomain of yeast Chd1 specifically interacts with methylated lysine 4 on histone H3 (H3K4me), and this chromodomain-mediated methyl-binding is required for enhanced acetylation activity of the SLIK complex on methylated substrates both in vitro and in vivo. Chd1 was identified as a component of the SAGA and SLIK histone acetyltransferase complexes. |
Co-purification/mass spectrometry, in vitro acetylation assay with methylated substrate, chromodomain binding assays, in vivo functional studies |
Nature |
High |
15647753
|
| 2005 |
Human CHD1 (but not yeast Chd1) directly and selectively binds histone H3 methylated at lysine 4 (H3K4me2/me3) via its tandem chromodomains acting cooperatively; both chromodomains are required for this recognition, with Kd ~5 µM for di- and trimethyl H3K4. |
In vitro binding studies, dissociation constant measurements, domain mutagenesis/truncation analysis |
The Journal of biological chemistry |
High |
16263726
|
| 2003 |
Yeast Chd1 functions during transcription elongation: it interacts with Rtf1 (Paf1 complex), and with elongation factors Spt4-Spt5 and Spt16-Pob3 (FACT), and associates with actively transcribed chromatin regions. Deletion of CHD1 suppresses cold-sensitive spt5 mutations also suppressed by Paf1 complex defects. |
Two-hybrid screen, co-immunoprecipitation, genetic epistasis (suppressor analysis), chromatin immunoprecipitation |
The EMBO journal |
High |
12682017
|
| 2005 |
CHD1 functions as an ATP-dependent chromatin assembly factor that, together with NAP1 chaperone and core histones, assembles regularly spaced nucleosomes by a processive mechanism. CHD1 exists predominantly as a monomer and assembles chromatin with shorter nucleosome repeat length than ACF; unlike ACF, CHD1 cannot assemble chromatin containing histone H1. |
In vitro chromatin assembly assay with purified components (CHD1, NAP1, core histones, relaxed DNA), nucleosome spacing analysis |
Nature structural & molecular biology |
High |
15643425
|
| 2007 |
CHD1 (Drosophila) is required for incorporation of histone variant H3.3 into the male pronucleus during early embryogenesis. CHD1 interacts with HIRA (H3.3 chaperone) in cytoplasmic extracts. Loss of CHD1 abolishes H3.3 incorporation and renders the paternal genome unable to participate in zygotic mitoses, leading to haploid embryos. |
Genetic loss-of-function (CHD1 elimination in Drosophila embryos), immunofluorescence for H3.3 incorporation, co-immunoprecipitation of CHD1 with HIRA from cytoplasmic extracts |
Science (New York, N.Y.) |
High |
17717186
|
| 2009 |
Chd1 is required to maintain open/euchromatin in mouse embryonic stem cells. Downregulation of Chd1 leads to accumulation of heterochromatin, loss of pluripotency (inability to give rise to primitive endoderm, propensity for neural differentiation), and reduced efficiency of somatic cell reprogramming. Chd1 associates with promoters of active genes. |
RNAi knockdown, chromatin immunoprecipitation, differentiation assays, reprogramming assays |
Nature |
High |
19587682
|
| 2009 |
CHD1 binds to SSRP1 (a subunit of the FACT complex) both in vivo and in vitro, localizes to centromeres in a CENP-H-containing complex-dependent manner, and is required for deposition of newly synthesized CENP-A into centromeric chromatin. RNAi knockdown of CHD1 decreases centromere-localized CENP-A levels. |
Co-immunoprecipitation (in vivo and in vitro), conditional mutant cell lines, RNAi knockdown, immunofluorescence |
Molecular biology of the cell |
Medium |
19625449
|
| 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 (revealed by crystal structure). Disruption of the chromodomain-ATPase interface prevents discrimination between nucleosomes and naked DNA and reduces reliance on the histone H4 tail for nucleosome sliding. |
Crystal structure of Chd1 chromodomain region, site-directed mutagenesis, ATPase and nucleosome sliding assays |
Molecular cell |
High |
20832723
|
| 2011 |
The C-terminal DNA-binding domain of yeast Chd1 contains SANT and SLIDE domains (structural homologs of ISWI DNA-binding domains), is required for nucleosome binding and remodeling, and site-directed mutagenesis of conserved residues identifies those important for DNA binding. SLIDE domains were also identified in CHD6-9 proteins. |
Crystal structure of Chd1 DNA-binding domain, site-directed mutagenesis, nucleosome binding and remodeling assays |
The EMBO journal |
High |
21623345
|
| 2011 |
The DNA-binding domain of Chd1 is not essential for nucleosome sliding per se but is critical for centering mononucleosomes on short DNA fragments. Replacing the native DNA-binding domain with foreign DNA-binding domains (AraC or engrailed) redirects nucleosome sliding toward their cognate DNA sequences, demonstrating that the DNA-binding domain's affinity for extranucleosomal DNA determines the direction of Chd1-mediated nucleosome sliding. |
Domain-swap experiments with chimeric Chd1 constructs, nucleosome sliding assays, FRET-based positioning assays |
Molecular and cellular biology |
High |
21969605
|
| 2011 |
Crystal structure of Saccharomyces cerevisiae Chd1 DNA-binding domain in complex with DNA shows the SLIDE domain contacts the DNA major groove (in contrast to predicted minor-groove binding), with contacts predominantly on one DNA strand. The bound DNA duplex is straight, consistent with preference for extranucleosomal DNA. |
X-ray crystallography |
The Journal of biological chemistry |
High |
22033927
|
| 2012 |
Chd1 is required for maintenance of high levels of H2B monoubiquitination (H2BK123ub) genome-wide. Loss of Chd1 causes substantial reduction of H2BK123ub levels and reduced nucleosome occupancy in gene bodies, but does not affect H3K4 or H3K79 trimethylation patterns. This function is conserved from yeast to humans. |
Genome-wide ChIP-seq, western blot analysis of histone modifications in chd1Δ yeast and human CHD1-depleted cells |
Genes & development |
High |
22549955
|
| 2012 |
Isw1b and Chd1 act in conjunction to prevent trans-histone exchange over coding regions during transcription elongation. Chd1 is recruited to open reading frames by H3K36 methylation context and maintains chromatin integrity during RNAPII passage. |
Genome-wide nucleosome mapping, histone exchange assays, genetic epistasis in S. cerevisiae, in vivo and in vitro H3K36me recruitment assays |
Nature structural & molecular biology |
High |
22922743
|
| 2013 |
CHD1 is required for efficient recruitment of androgen receptor (AR) to responsive promoters in prostate cells. Inactivation of CHD1 in vitro prevents formation of ERG rearrangements by impairing AR-dependent transcription. CHD1 regulates expression of AR-responsive tumor suppressor genes including NKX3-1, FOXO1, and PPARγ. |
RNAi knockdown, chromatin immunoprecipitation for AR, gene expression analysis, FISH for ERG rearrangements |
Cancer research |
Medium |
23492366
|
| 2014 |
Chd1 is recruited to promoter-proximal nucleosomes of actively transcribed genes and is responsible for the majority of RNAPII-directed nucleosome turnover at these sites. Expression of a dominant-negative Chd1 increases stalling of RNAPII past the entry site of promoter-proximal nucleosomes. Chd1 evicts nucleosomes downstream of the promoter to overcome the nucleosomal barrier and enable RNAPII promoter escape. |
Modified ChIP using micrococcal nuclease digestion, dominant-negative Chd1 expression, RNAPII stalling assays |
eLife |
High |
24737864
|
| 2016 |
Dimethylation of KDM1A at K114 (K114me2) by EHMT2 creates a binding site for CHD1. Co-crystal structure of CHD1 with KDM1A K114me2 peptide characterizes the recognition mode. Genome-wide analyses reveal chromatin co-localization of KDM1A K114me2, CHD1, and androgen receptor (AR) in prostate tumor cells, linking this assembly to AR-dependent transcription and TMPRSS2-ERG fusion formation. |
Co-crystal structure (X-ray crystallography), genome-wide ChIP-seq, in vitro binding assays, functional assays for TMPRSS2-ERG translocation |
Nature structural & molecular biology |
High |
26751641
|
| 2016 |
CHD1 and ISW1 compete to set nucleosome spacing in vivo on most yeast genes, with CHD1 directing shorter spacing and ISW1 directing longer spacing. CHD1-directed short spacing correlates with eviction of linker histone H1, while ISW1-directed longer spacing allows H1 binding and chromatin condensation. |
Genome-wide nucleosome sequencing in single and double deletion strains, linker histone H1 occupancy mapping |
Nucleic acids research |
High |
26861626
|
| 2016 |
The Chd1 chromatin remodeler requires H2A/H2B on the entry side of the nucleosome for sliding. When presented with hexasomes (lacking one H2A/H2B dimer), Chd1 shifts them unidirectionally rather than bidirectionally. Ubiquitin-conjugated H2B on the entry side stimulates nucleosome sliding by Chd1. |
Reconstituted hexasome and asymmetric nucleosome sliding assays, single-molecule imaging, ubiquitinated H2B functional assays |
eLife |
High |
28032848
|
| 2017 |
Cryo-EM structure of yeast Chd1 bound to a nucleosome at 4.8 Å resolution. Chd1 detaches two turns of DNA from the histone octamer. The SANT and SLIDE domains contact detached DNA around SHL -7 of the first DNA gyre. The ATPase motor binds the second DNA gyre at SHL +2 and is anchored to the N-terminal tail of histone H4. The double chromodomain swings toward nucleosomal DNA at SHL +1, causing ATPase closure. The ATPase promotes DNA translocation toward the nucleosome dyad. |
Cryo-electron microscopy structure determination |
Nature |
High |
29019976
|
| 2017 |
Site-specific cross-linking shows that Chd1 chromodomains and ATPase motor bind to adjacent SHL1 and SHL2 sites on nucleosomal DNA and pack against the DNA-binding domain on exiting DNA. This domain arrangement spans both DNA gyres and bridges both ends of a ~90-bp nucleosomal loop, suggesting a mechanism for nucleosome assembly and spacing. |
Site-specific cross-linking, biochemical domain mapping, structural modeling |
Molecular cell |
High |
28111016
|
| 2017 |
Monomeric Chd1 shifts nucleosomal DNA bidirectionally by dynamically alternating between different segments of the nucleosome. Sliding generates unstable remodeling intermediates that spontaneously relax. The DNA-binding domain and chromodomains are two regulatory domains controlling sliding: the chromodomains play a key role in substrate discrimination. |
Single-molecule FRET, nucleosome sliding assays with truncation and mutation constructs |
Molecular cell |
High |
28943314
|
| 2017 |
PTEN stimulates GSK3β-mediated phosphorylation of CHD1 degron domains, promoting CHD1 degradation via the β-TrCP-mediated ubiquitination-proteasome pathway. PTEN deficiency results in CHD1 stabilization, which then engages trimethyl H3K4 to activate the TNF-NF-κB gene network. |
Biochemical phosphorylation assays, ubiquitination assays, proteasome inhibitor experiments, CHD1 degron mutagenesis, ChIP for H3K4me3 |
Nature |
High |
28166537
|
| 2017 |
CHD1 is required for early DNA double-strand break repair via homologous recombination. CHD1 loss leads to reduced H2AX phosphorylation (γH2AX), impaired CtIP recruitment to DSB sites, reduced H2AX incorporation and poor retention at DSBs. The N-terminal region of CHD1 inhibits its own DNA binding, ATPase, and chromatin assembly/remodeling activities. |
CRISPR/Cas9 CHD1 knockout in human cells, γH2AX ChIP, HR repair assays, CtIP recruitment assays, ATPase and chromatin remodeling assays with N-terminal truncation constructs |
Nucleic acids research |
High |
29529298
|
| 2017 |
CHD1 promotes the XPC-to-TFIIH handover of nucleosomal UV lesions during global-genome nucleotide excision repair (GG-NER). CHD1 is recruited to UV lesions in a nucleosome/histone context in an XPC-dependent manner. CHD1 depletion slows CPD excision and sensitizes cells to UV-induced cytotoxicity. |
Chromatin immunoprecipitation of chromatin fragments, chromatin fractionation, immunofluorescence, CHD1 depletion with UV sensitivity assays |
The EMBO journal |
Medium |
29018037
|
| 2018 |
Cryo-EM structures of yeast Chd1 bound to nucleosomes with ADP-beryllium fluoride (transition state mimic) reveal conserved contacts with single-strand translocases plus unique contacts with both DNA strands. Two turns of linker DNA are prised off the histone octamer upon Chd1 binding, and both the histone H3 tail and ubiquitin conjugated to H2B K120 are reoriented toward the unraveled DNA. |
Cryo-electron microscopy structure determination with transition state mimic |
eLife |
High |
30079888
|
| 2018 |
The Chd1 ATPase motor stimulates DNA unwrapping from the edge of the nucleosome in a nucleotide-dependent and DNA sequence-sensitive fashion. Different nucleotide analogs (AMP-PNP vs. ADP·BeF3-) produce distinct DNA conformations: AMP-PNP causes in-plane DNA unwrapping, while ADP·BeF3- shows out-of-plane unwrapping. The Chd1 DNA-binding domain is not required for unwrapping. |
Stopped-flow binding kinetics, bulk FRET, small-angle X-ray scattering with contrast variation |
Nucleic acids research |
High |
29850894
|
| 2019 |
CHD1 occupies prostate-specific enhancers enriched for androgen receptor (AR) and lineage-specific cofactors. Upon CHD1 loss, the AR cistrome is redistributed to an oncogenic pattern, driving tumor formation in the murine prostate. CHD1 constrains AR binding/function to limit tumor progression. |
ChIP-seq for CHD1 and AR in human and mouse cells, CHD1 knockout/knockdown with ATAC-seq, in vivo mouse prostate tumor models |
Cancer cell |
High |
30930119
|
| 2016 |
CHD1 loss impairs CtIP recruitment to chromatin and subsequent DNA end resection during DSB repair, specifically affecting homologous recombination (HR) but not non-homologous end joining (NHEJ). CHD1 is proposed to open chromatin around DSBs to facilitate HR protein recruitment. |
CHD1 siRNA/shRNA depletion, CtIP chromatin recruitment assays, HR and NHEJ repair assays, PARP inhibitor sensitivity tests |
EMBO reports |
Medium |
27596623
|
| 2021 |
Biochemical reconstitution shows Chd1 and FACT together facilitate Pol II transcription through a nucleosome when elongation factors Spt4/5 and TFIIS are present. Cryo-EM structures reveal: (1) Pol II transcription exposes the proximal H2A-H2B dimer bound by Spt5, with Chd1 poised to pump DNA toward Pol II via its released inhibitory DNA-binding region; (2) a partially unraveled nucleosome generated by Pol II binds FACT, which excludes Chd1 and Spt5, enabling FACT-histone transfer to upstream DNA. |
Biochemical reconstitution of Pol II transcription through nucleosomes, cryo-EM structure determination of transcribing complexes |
Nature structural & molecular biology |
High |
33846633
|
| 2021 |
Chd1 interacts with DNA repair factors including Atm, Parp1, Kap1, and Topoisomerase 2β. In Chd1 KO embryonic stem cells, DNA double-strand breaks accumulate specifically at Chd1-bound Pol II-transcribed genes (particularly longer genes with GC-rich promoters) and rDNA. |
Co-immunoprecipitation of Chd1 with repair factors, DSB mapping (BLISS/END-seq) in Chd1 KO ES cells, ChIP-seq |
Nature communications |
Medium |
34381042
|
| 2021 |
Chd1 is required for FACT spreading from the +1 nucleosome to downstream nucleosomes during transcription. FACT binds the +1 nucleosome as it is partially unwrapped by engaging RNAPII, and spreads to downstream nucleosomes aided by Chd1. |
High-resolution genome-wide mapping (MNase-ChIP-seq), single-molecule tracking, mathematical modeling, genetic deletion of Chd1 |
Molecular cell |
High |
34380014
|
| 2020 |
CHD1 loss results in global changes in open and closed chromatin (ATAC-seq) with associated transcriptomic changes, establishing transcriptional plasticity that enables antiandrogen resistance through four transcription factors (NR3C1, POU3F2, NR2F1, TBX2). |
In vivo shRNA screen, ATAC-seq, RNA-seq, CRISPR-based functional screening |
Cancer cell |
Medium |
32220301
|
| 2020 |
CHD1 regulates IL6 transcription, and IL6 is a key transcriptional target of CHD1 involved in recruitment of myeloid-derived suppressor cells (MDSCs) to reshape the tumor microenvironment in PTEN-deficient prostate cancer. Prostate-specific deletion of Chd1 in PTEN-deficient mouse models delays tumor progression and reduces MDSC recruitment. |
Genetically engineered mouse models (Pten and Pten/Smad4 with prostate-specific Chd1 deletion), tumor microenvironment immunophenotyping, IL6 ChIP and expression analysis |
Cancer discovery |
Medium |
32385075
|
| 2022 |
Cryo-EM structure of Chd1 bound to a nucleosome in a nucleotide-free state at 2.3 Å resolution reveals that Chd1 stimulates the nucleosome to absorb an additional nucleotide on each DNA strand at two different locations. On the tracking strand within the ATPase binding site, this extra nucleotide induces a local A-form DNA geometry, explaining sequential ratcheting of each strand. A histone-binding motif (ChEx) is identified that can block opposing remodelers and may allow Chd1 to participate in histone reorganization during transcription. |
Cryo-electron microscopy at 2.3 Å resolution, structural analysis |
Nature structural & molecular biology |
High |
35173352
|
| 2024 |
Cryo-EM structures of Chd1 bound to a hexasome-nucleosome complex show Chd1 positions its ATPase domain to shift the hexasome away from the nucleosome. In the absence of the inner H2A/H2B dimer, Chd1's DNA-binding domain packs against the ATPase domain (inhibited state). Restoration of the H2A/H2B dimer by FACT triggers DBD rearrangement that displaces the DBD and stimulates Chd1 remodeling, demonstrating FACT-Chd1 cooperation in resolving transcription-induced hexasome-nucleosome complexes. |
Cryo-EM structure determination of two states (before and after FACT-mediated H2A/H2B restoration), biochemical reconstitution |
Molecular cell |
High |
39270644
|
| 2021 |
Chd1 disruption in Drosophila heads results in reduced H3.3 levels, perturbed brain chromatin structure, and global de-repression of transcription, with phenotypic consequences of reduced food intake, metabolic alterations, and shortened lifespan. Strong genetic interaction between Chd1 and H3.3 chaperone HIRA was demonstrated. |
Quantitative mass spectrometry for histone variant levels, genetic interaction analysis (double mutants), brain-specific rescue experiments, ChIP |
Cell reports |
Medium |
34610319
|
| 2021 |
Autoinhibitory elements of Chd1 (chromodomains and 'bridge') act together to block nucleosome sliding by preventing initiation of twist defects when the DNA-binding domain is not bound to entry-side DNA. These elements target nucleotide-free and ADP-bound states of the ATPase motor, favoring a partially disengaged ATPase-nucleosome state. |
Biochemical nucleosome sliding assays with Chd1 mutants lacking autoinhibitory elements, kinetic analysis, nucleotide-state specific assays |
Proceedings of the National Academy of Sciences of the United States of America |
High |
33468676
|
| 1999 |
Both the chromodomain (C) and ATPase/helicase-like domain (H) of CHD1 are essential for its proper association with chromatin. CHD1 interacts with SSRP1 (an HMG box-containing protein/FACT subunit) through an N-terminal segment that does not include the chromodomain. |
Transient transfection with wild-type and domain-mutant CHD1 constructs, immunocytochemistry, co-immunoprecipitation |
Chromosoma |
Medium |
10199952
|
| 1995 |
CHD1 preferentially binds relatively long A-T tracts in double-stranded DNA via minor-groove interactions. The DNA-binding activity maps to a 229-amino-acid C-terminal segment. CHD1 is a constituent of bulk chromatin extractable with 0.6 M NaCl or EDTA after MNase digestion. CHD1 is released into the cytoplasm when cells enter mitosis and is reincorporated into chromatin during telophase-cytokinesis. |
DNA binding assays, deletion mapping, chromatin fractionation, immunocytochemistry across cell cycle stages |
Molecular and cellular biology |
Medium |
7739555
|
| 2003 |
CHD1 co-immunoprecipitates with histone deacetylase (HDAC) activity and associates with NCoR (a transcriptional corepressor) in yeast two-hybrid and in vitro pull-down assays. CHD1 also interacts with splicing proteins mKIAA0164, Srp20, and SAF-B by two-hybrid, and CHD1 overexpression affects alternative splicing. |
Co-immunoprecipitation (for HDAC), yeast two-hybrid and in vitro pull-down (for NCoR and splicing proteins), alternative splicing assays |
Biochemical and biophysical research communications |
Low |
12890497
|
| 2011 |
Mediator coactivator complex is required for CHD1 recruitment to preinitiation complexes on chromatin. CHD1 is recruited to naive chromatin but shows enhanced recruitment on H3K4me3 chromatin. CHD1 co-immunoprecipitates with Mediator components from cell extracts, and this interaction is abolished by knockdown of a specific Mediator subunit. |
MuDPIT proteomic analysis of purified preinitiation complexes, immunoblot, shRNA depletion, co-immunoprecipitation, genome-wide binding (ChIP-seq in mouse ES cells) |
Genes & development |
High |
21979373
|
| 2016 |
CHD1 interacts with the influenza virus polymerase complex. CHD1 downregulation reduces viral polymerase activity, viral RNA transcription, and production of infectious particles. CHD1 associates with RNAPII and undergoes parallel degradation with RNAPII during influenza infection. |
Co-immunoprecipitation of CHD1 with viral polymerase, CHD1 knockdown with viral replication assays, co-localization immunofluorescence |
Journal of virology |
Medium |
26792750
|