Omics · study · 2026
KMT2D-Mediated H3K4methylation is Essential for GATA1 Transcriptional Activation in Erythropoiesis [ChIP-seq]
Listed in NCBI GEO
The regulation of enhancer activity is essential for cell differentiation and different diseases.
Description
KMT2D is considered a significant histone methyltransferase that catalyzes H3K4me1 on enhancers and activates the enhancers by recruiting acetyltransferase for H3K27ace. However, how exactly enhancer activation is determined in human erythropoiesis remains incompletely understood.
Here, by using an unbiased genetic screen in human erythroblasts, we identified and verified that KMT2D is an essential factor for human erythropoiesis. Accordingly, we observed that KMT2D is indispensable for the activation of erythroid signature genes. Moreover, to further study the direct transcriptional regulatory role of KMT2D, we employed the auxin-inducible degron 2 (AID2) system in human erythroblast cell lines to systematically investigate the effects of acute depletion of KMT2D on transcriptional programs, the genome-wide occupancy of KMT2D and the erythroid master regulator GATA1.
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Importantly, we revealed that KMT2D colocalized with GATA1 on more than one thousand active enhancers. Moreover, the GATA1 and KMT2D co-localized enhancers exhibit significant higher activities relative to the GATA1 only occupied enhancers. After the depletion of KMT2D, the active histone marks on those enhancers were significantly reduced in accompanying with suppression of the selective targets of GATA1, including numerous erythroid genes (such as ZFPM1, SLC4A1, and EPOR).
These results suggest that KMT2D is indispensable for the activation of erythroid gene expression by GATA1. Thus, our results revealed a novel role of KMT2D in the selective dependency of GATA1 on active enhancers, which could impact the transcriptional regulation of KMT2D in both hematopoiesis and blood cancers.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE293nnn/GSE293474 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE293474 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1244765 ncbi.nlm.nih.gov/bioproject/PRJNA1244765 ↗
project · from NCBI GEO
- PubMed 42409830 pubmed.ncbi.nlm.nih.gov/42409830 ↗
publication · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens
- From keywords
- Life Sciences
Provenance · 1 source records, 7 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE293474 | 12 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| concepts[method].geo_series_type:genome-binding-occupancy-profiling-by-high-throughput-sequencing | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /gdstype |
| concepts[organism].NCBITaxon:9606 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| description | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /summary |
| publication_date | source · NCBI GEO | connector:ncbi_geo@1.0.0 | |
| title | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /title |