Data · dataset · 2026
Investigating BTK inhibition-related epigenetic mechanisms and the role of TRIM24 ni CD5+ malignant B cells
Listed in ZivaHub and Deakin Research Online and DMU Figshare — shown once because both records carry DOI 10.17034/32640225.v1
BTK inhibition (BTKi) by ibrutinib (IB) represents a significant advancement in treating CD5+'B cell malignancies like Chronic Lymphocvtic Leukemia (CLL) and Mantle Cell Lymphoma (MCL).
Description
Recent studies indicate that BTKimodifies epigenomic and transcriptomic dynamics in CLL, prompting us to explore these effects globally and at a gene-specific level. We sequenced a matched CLL sample (pre- and post-IB treatment) using the promoter Capture HiC methodology, revealing strong enrichments of long-distance peaks associated with various genomic features and a notable downregulation following BTKi.
By intersecting these peaks with differentially altered genes (RNA-seq) and active enhancer marks (H3K27ac ChIP-seq), we identified a refined list of overlapping genes that illustrated the cell states before and after IB treatment. Additionally, we detected 255 differentially altered H3K4me1 peaks in MEC-1 CLL cells after 48 hours of IB treatment using Cut&Run sequencing. Among the top candidates from our high-throughput screening, TRIM24 emerged as a key epigenetically regulated gene upon ibrutinib therapy.
Read the rest (3 more)
We found a significant long-range interaction gained upstream of the TRIM24 promoter post-IB treatment, correlating with increased mRNA and protein expression in CLL cells and cell lines. This was accompanied by translocation of the protein into the nuclear compartment in vitro. Similar trends were observed in MCL cell models, with the effects to be IB-specific.
Furthermore, knockdown and CRISPR-Cas9 knockout models of TRIM24 demonstrated its critical role in the DNA damage response, as loss of TRIM24 sensitized CL and MCL cells to BTKi. The functional inhibition of TRIM24 ni combination with IB produced a synergistic cytotoxic effect. Overall, these findings indicate that BTKi alters 3D interactions and histone dynamics ni the epigenome, influencing the transcriptome.
Acharacteristic example is TRIM24, showing that its expression and function is regulated by the BTKi-driven epigenetic changes and could be exploited for therapy.<br><br><i>Thesis embargoed until 31 December 2029.</i>
Links
Where it is published
- DOI doi.org/10.17034/32640225.v1 ↗
DOI / persistent id · from zivahub uct ac za
Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
metadata API · from zivahub uct ac za
Topics
- From keywords
- Earth & Environmental Science · Earth & Environmental Science · Earth & Environmental Science · Epigenetics · Epigenetics · Epigenetics · Life Sciences · Life Sciences · Life Sciences
- Inferred from text
- RNA sequencing 65% · Sequencing 75%
Provenance · 3 source records, 16 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ZivaHub | oai:figshare.com:article/32640225 | 7 d ago | JSON v1 |
| Deakin Research Online | oai:figshare.com:article/32640225 | 7 d ago | JSON v1 |
| DMU Figshare | oai:figshare.com:article/32640225 | 7 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].anzsrc:field:310504 | mapping · dro deakin edu au | vocabulary-mapper@1.0.0 | keywords['epigenetics'] |
| concepts[field].anzsrc:field:310504 | mapping · zivahub uct ac za | vocabulary-mapper@1.0.0 | keywords['epigenetics'] |
| concepts[field].anzsrc:field:310504 | mapping · figshare dmu ac uk | vocabulary-mapper@1.0.0 | keywords['epigenetics'] |
| concepts[field].local:field:earth-environmental | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · figshare dmu ac uk | connector:figshare_dmu_ac_uk@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · dro deakin edu au | connector:dro_deakin_edu_au@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · figshare dmu ac uk | connector:figshare_dmu_ac_uk@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · dro deakin edu au | connector:dro_deakin_edu_au@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[modality].local:modality:rna-seq | enrichment · zivahub uct ac za | keyword-concept-rules@1.0.0 | title+description (65%) |
| concepts[modality].local:modality:sequencing | enrichment · zivahub uct ac za | keyword-concept-rules@1.0.0 | title+description (75%) |
| description | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/description |
| license_text | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| publication_date | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| title | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/title |