Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HELLS is required for DNA methylation at human satellite repeats [RNA-seq]

ABSTRACT: HELLS is a known chromatin remodeler, but its specific genomic targets have not been sufficiently described. Here, we report the generation of HELLS knockout human pluripotent cells and through telomere-to-telomere mapping of whole genome bisulfite sequencing data combined with ATAC-sequencing, we discovered a striking loss of DNA methylation over inaccessible, satellite repeats. Our study further clarifies the role of HELLS and provides insights into functional consequences through its deregulation in diseases.

ORGANISM(S): Homo sapiens

PROVIDER: GSE296398 | GEO | 2025/06/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

The role of HELLS in human induced pluripotent stem cells II

Project description:interactions that require remodeling proteins like the Helicase, Lymphoid-specific (HELLS). Here, we generate HELLS and de novo DNA methyltransferase 3 A and B (DNMT3A/B) knockout hu-man pluripotent stem cells and assemble telomere-to-telomere maps of whole genome bisulfite sequencing data combined with ATAC-sequencing. Disrupting HELLS induces a global loss of DNA methylation that is distinct from the de novo DNMTs, in particular over peri/centromeric satellite repeats as defined in the telomere-to-telomere genome assembly. However, HELLS is dispensable for local enhancer remodeling and the potential to differentiate into the three germ layers. Taken together, these findings further clarify the genomic targets and role of HELLS in human cells.

2025-06-23 | GSE250465 | GEO

The role of HELLS in human induced pluripotent stem cells

Project description:DNA methylation is essential for genome integrity and involves multi-layered chromatin interac-tions that require remodeling proteins like the Helicase, Lymphoid-specific (HELLS). Here, we generate HELLS and de novo DNA methyltransferase 3 A and B (DNMT3A/B) knockout human pluripotent stem cells and assemble telomere-to-telomere maps of whole genome bisulfite se-quencing data combined with ATAC-sequencing. Disrupting HELLS induces a global loss of DNA methylation that is distinct from the de novo DNMTs, in particular over peri/centromeric satellite repeats as defined in the telomere-to-telomere genome assembly. However, HELLS is dispen-sable for local enhancer remodeling and the potential to differentiate into the three germ layers. Taken together, these findings further clarify the genomic targets and role of HELLS in human cells.

2025-06-23 | GSE241688 | GEO

HELLS is required for DNA methylation at human satellite repeats

Project description:HELLS is required for DNA methylation at human satellite repeats

| PRJNA1055544 | ENA

HELLS is required for DNA methylation at human satellite repeats [RNA-seq]

Project description:HELLS is required for DNA methylation at human satellite repeats [RNA-seq]

| PRJNA1259059 | ENA

Impact of Hells loss-of-function on DNA methylation in B cells during humoral immune responses: kinetic comparison of Mb1-Hells knockout and control mice by enzymatic-methyl sequencing

Project description:We are interested in deciphering the mechanism by which DNA methylation in late B cell differentiation affects humoral immune response. We were using enzymatic-methyl sequencing (EM-seq) and chose to study a very rare immunodeficiency called ICF type 4, where a point mutation in a gene encoding the protein HELLS causes a lack of both circulating antibodies and memory B cells in human. HELLS is a chromatin remodeler, that allows for DNA methylation to occur.

2023-07-27 | E-MTAB-12609 | biostudies-arrayexpress

Chromatin regulator HELLS mediates SSB repair and responses to DNA alkylation damage

Project description:The SNF2 family chromatin remodeler HELLS has emerged as an important regulator of cell proliferation, genome stability, and several cancer pathways. Significant upregulation of HELLS has been reported in 33 human cancer types. While HELLS has been implicated in DNA damage response, its function in DNA repair is poorly understood. Here we report a new regulatory link between HELLS and single-strand break (SSB) repair in cellular responses to DNA alkylation damage. We found that loss of HELLS impairs SSB repair, and selectively sensitizes cells to DNA alkylating agents and PARP inhibitors (PARPi). Furthermore, we found that HELLS is co-expressed with PARP1 in cancer cells, and its loss is synthetic lethal with homologous recombination deficiency (HRD). This work unveils new functions of HELLS in modulating SSB repair and responses to clinically relevant DNA alkylation damage, thus offering new insights into the potential therapeutic value of targeting HELLS in cancer.

2025-07-01 | GSE283831 | GEO

Impact of Hells loss-of-function on DNA methylation in B cells during humoral immune responses: kinetic comparison of Mb1-Hells knockout and control mice by single-cell RNA sequencing

Project description:We are interested in deciphering the mechanism by which DNA methylation in late B cell differentiation affects humoral immune response. We chose to study a very rare immunodeficiency called ICF type 4, where a point mutation in a gene encoding the protein HELLS causes a lack of both circulating antibodies and memory B cells in human. HELLS is a chromatin remodeler, that allows for DNA methylation to occur. Using a Hells conditional knock-out in B cells, we measured the kinetics of the immune B cell response, following immunization with NP-CGG, and show a lack of memory and plasma cells accompanied by a defect in germinal center maintenance, but not by its formation. Single cell RNAseq of cell sorted naive, germinal center B cells and memory B cells at day 7 and day 14 post NP-immunization helped us better characterize the phenotype.

2023-07-25 | E-MTAB-12499 | biostudies-arrayexpress

HELLS and PRDM9 from a pioneer complex to open chromatin at meiotic recombination hotspots

Project description:Chromatin barriers prevent spurious interactions between regulatory elements and DNA-binding proteins. One such barrier, whose mechanism for overcoming is poorly understood, is access to recombination hotspots during meiosis. Here we identify that the DNA-binding protein PRDM9 and chromatin remodeler HELLS function together to open chromatin at hotspots providing access to the DNA double-strand break (DSB) machinery. Recombination hotspots are decorated by a unique combination of histone modifications, not found at other regulatory elements. HELLS is recruited by PRDM9, and is necessary for both histone modification and DNA accessibility at hotspots. In male mice lacking HELLS, DSBs are retargeted to other sites of open chromatin, leading to germ cell death and sterility. Together, these data provide a model for hotspot activation where HELLS and PRDM9 function as a pioneer complex to create a unique epigenomic environment to open chromatin in preparation for proper placement and repair of DSBs.

2019-12-17 | GSE135896 | GEO

The C-terminal 4CXXC-type zinc finger domain of CDCA7 recognizes hemimethylated DNA and modulates activities of chromatin remodeling enzyme HELLS

Project description:The chromatin-remodeling enzyme helicase lymphoid-specific (HELLS) interacts with cell division cycle-associated 7 (CDCA7) on nucleosomes and is involved in the regulation of DNA methylation in higher organisms. Mutations in these genes cause immunodeficiency, centromeric instability, and facial anomalies (ICF) syndrome, which also results in DNA hypomethylation of satellite repeat regions. We investigated the functional domains of human CDCA7 in HELLS using several mutant CDCA7 proteins. The central region is critical for binding to HELLS, activation of ATPase, and nucleosome sliding activities of HELLS-CDCA7. The N-terminal region tends to inhibit ATPase activity. The C-terminal 4CXXC-type zinc finger domain contributes to CpG and hemimethylated CpG DNA preference for DNA-dependent HELLS-CDCA7 ATPase activity. Furthermore, CDCA7 showed a binding preference to DNA containing hemimethylated CpG, and replication-dependent pericentromeric heterochromatin foci formation of CDCA7 with HELLS was observed in mouse embryonic stem cells; however, all these phenotypes were lost in the case of an ICF syndrome mutant of CDCA7 mutated in the zinc finger domain. Thus, CDCA7 most likely plays a role in the recruitment of HELLS, activates its chromatin remodeling function, and efficiently induces DNA methylation, especially at hemimethylated replication sites.

2024-06-23 | GSE270227 | GEO

The ZBTB24-CDCA7 axis regulates HELLS enrichment at centromeric satellite repeats to facilitate DNA methylation.

Project description: Not available

| S-EPMC7026229 | biostudies-literature