EBF1 (EBF Transcription Factor 1)

EBF1 presented a promoter hypermethylation pattern in COAD cell lines, in which its expression was restored upon treatment of the methylation inhibitor 5-azacytidine. In conclusion, this study highlights that the hypermethylation of EBF1 leads to transcription activation of DEPDC1B, which promotes cell cycle progression, EMT, and malignant progression in COAD. Restoring EBF1 levels or suppressing DEPDC1B expression may be promising strategies for COAD management.

Our findings underscore the significant role of rare, high-penetrance genetic variants in FLC susceptibility, particularly in mucin glycosylation and DNA repair genes. These findings offer promising targets for early detection and personalized therapies.

In this exploratory analysis, we identified differentially methylated loci linked to thyroid cancer in Agent Orange exposed Veterans. Further research is necessary to replicate our findings in a larger cohort including Agent Orange exposure determination through biomarker assessment, and to elucidate mechanisms behind these associations in in vitro exposure models.

Mechanistically, we discovered that enhancer positioning at local topological centres is required for promoter engagement, with EBF1 acting as a permeable barrier to loop-extruding cohesin at enhancers. Extending these findings to T cell leukaemia, we show that lineage-determining transcription factors such as EBF1 and TCF1 radially position enhancers within gene loci to enable multi-enhancer regulation of key oncogenes at the single-allele level.

The drug-resistant subcluster of Pro-B cells was characterized by high expression of RPS29, B2M, RPL41, RPS21, NEIL1, AC007384.1, and CRIM1, as well as enrichment of the B cell receptor signaling pathway. Our study identified distinct cellular subpopulations associated with treatment failure, provide insights into the molecular mechanisms underlying treatment resistance in B-ALL and may inform the development of targeted therapies for high-risk patients.

Mechanistically, we found that positioning of enhancers at allelic topological centers is required for their interactions with target promoters, with EBF1 serving as a barrier to the loop-extruding cohesin on enhancers. These findings, which we demonstrate their generalizability to the T-cell-lineage-determining transcription factor TCF1 in T-cell leukemia, suggest that lineage-determining transcription factors radially position enhancers and promoters to enable multi-enhancer regulation of key oncogenes.

Differences in hallmark gene set categories reflected distinct methylation and miRNA expression profiles. Overall, this integrative analysis mapped the intricate epigenetic landscape of BLBC, emphasizing the role of FFLs as regulatory motifs that integrate DNA methylation, TFs, and miRNAs in orchestrating disease's development and progression and offering potential targets for future diagnostic and therapeutic strategies.

Additional genetic alterations, termed "secondary hits" are involved in lymphoid development and pathogenesis of ALL. The most frequently observed rearrangements in TCF3 are: PAX5, IKZF1, SETDB2, EBF1, as well as CDKN2A/B.

A subset of the 14 markers could distinguish B- and T-ALL in an independent cohort of patients with ALL. This study can enhance our knowledge of the transcriptomic profile of different ALL subtypes.

The study integrates bioinformatics and single-cell RNA sequencing to reveal the role of memory B cells in ATB progression and TNFi treatment, offering insights into TNFi-associated TB susceptibility and potential therapeutic targets.

On the contrary, EBF1 is a flexible regulatory factor that exhibits diverse functional characteristics and regulatory models according to the different types of tumors and their microenvironment differences. This review elucidates the unique function of EBF1 in various solid tumors and associated signaling pathways, offering a theoretical foundation for a thorough comprehension of EBF1's intricate roles in solid tumor development.

Finally, when treated with the Bruton tyrosine kinase inhibitor ibrutinib, these silenced enhancers are relatively stable during therapy compared with the CLL-gained enhancers. In summary, we described an epigenetic silencing mechanism mediated by the heterochromatin that persists throughout CLL disease development and treatment and which may increase the risk of severe infections in MBL and CLL.