Omics · study · 2026
Concentration by histone readers MLLT1 and MLLT3 confers locus specificity to AID activity [ChIP-seq]
Listed in NCBI GEO
Activation-induced deaminase (AID) drives antibody diversification through class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes, but its mutagenic activity at several hundred other genes and enhancers contributes to B cell lymphoma.
Description
Despite its physiological and pathological relevance, how AID selectively mutates the Ig and a restricted set of off-target genes is unknown. Transcription is required for AID activity, but most transcribed genes are not mutated, and AID occupies more loci than it mutates.
Here, we identify the Super Elongation Complex (SEC) histone readers MLLT1 and MLLT3 as determinants of selective AID activity. Combined loss of MLLT1 and MLLT3 abolishes all AID-dependent processes, phenocopying AID deficiency. AID-mutated genomic regions are precisely marked by high MLLT1 and MLLT3 occupancy (MLLT1/3high) in mouse and human B cells, while nascent transcription remains largely unchanged in MLLT1- or MLLT3-deficient cells, indicating a direct role in licensing AID activity.
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Mechanistically, MLLT1 and MLLT3 are dispensable for global AID chromatin tethering but link AID to transcription elongation. In mice, both readers bind AID and are partially redundant, but MLLT1 plays a dominant role through its intrinsically disordered region, which promotes condensate formation and selectively concentrates AID. Fusing AID to MLLT1 or MLLT3 is sufficient to restore CSR and mutagenesis in SEC-deficient cells.
These findings reveal how MLLT1/3high licenses AID at a restricted subset of genomic regions by spatially confining and concentrating its activity, likely through condensate-based mechanisms.
Links
Get the data
- GEO FTP directory ftp.ncbi.nlm.nih.gov/geo/series/GSE336nnn/GSE336330 ↗
download · from NCBI GEO
Where it is published
- GEO accession page ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE336330 ↗
landing page · from NCBI GEO
Documentation and papers
- PRJNA1481260 ncbi.nlm.nih.gov/bioproject/PRJNA1481260 ↗
project · from NCBI GEO
Topics
- Stated by source
- Genome binding/occupancy profiling by high throughput sequencing · Homo sapiens · Mus musculus
- From keywords
- Life Sciences
Provenance · 1 source records, 8 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| NCBI GEO | GSE336330 | 13 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:10090 | source · NCBI GEO | connector:ncbi_geo@1.0.0 | /taxon |
| 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 |