YEATS4 (YEATS domain-containing protein 4)

The combination of Sotorasib and HDAC inhibitors could be an effective treatment for KRAS-mutant lung cancer. ANP32A may serve as a biomarker for Sotorasib treatment.

High expression of YEATS4 fortifies fatty acid metabolism, enhances self-renewal and growth of ALDH+ breast cancer stem cells, and is correlated with poor prognosis of breast cancer patients, especially the ER+ subtype. Our work uncovers YEATS4 as an "amplifier" in the feedforward circuit of histone crotonylation and lipid metabolism underlying the stemness and cell proliferation, supporting the pursuit of YEATS4 as a potential target for breast cancer intervention.

In summary, YEATS4 could contribute to LPS progression in a subset of MDM2-amplified tumors, particularly in high-grade DDLPS. Its variable functional impact across models highlights the complexity of the 12q13-15 amplicon and supports further investigation into YEATS4 as a potential molecular marker and therapeutic target in LPS.

Molecular docking revealed that these compounds bound to the GAS41 YEATS domain pocket in a manner similar to Compounds 9 and 3b, providing a structural basis for exploring the selective inhibition of GAS41 as part of an essential molecular framework. Overall, our study illustrates the crucial role of GAS41 in glioma progression and the malignant phenotype and suggests that targeting GAS41 may be a promising therapeutic treatment strategy for gliomas.

Our study shows that reintervention is common after surgical myomectomy. Uterine leiomyomas typically develop independently, but some share a clonal origin. Repeat leiomyoma occurrence may be due to genetic predisposition, such as a germline FH mutation. Distinct somatic YEATS4 mutations identified in multiple leiomyomas from the same patient indicate a possible role for YEATS4 in repeat leiomyomas.

GAS41 knockout or H3K27cr-binding depletion results in p21 de-repression, cell-cycle arrest, and tumor growth inhibition in mice, explaining a causal relationship between GAS41 and MYC gene amplification and p21 downregulation in colorectal cancer. Our study suggests that H3K27 crotonylation signifies a previously unrecognized, distinct chromatin state for gene transcriptional repression in contrast to H3K27 trimethylation for transcriptional silencing and H3K27 acetylation for transcriptional activation.

Our data indicate that GAS41 mediates proliferation and GEM resistance in pancreatic cancer cells via H2A.Z.2 and Notch1.

Notably, four paralogous of human YEATS domain family members, namely eleven-nineteen-leukaemia (ENL), ALL1-fused gene from chromosome 9 protein (AF9), YEATS2 and glioma amplified sequence 41 (GAS41), have a strong link to cancer yet new findings also highlight a potential novel role in neurological diseases. Here, in an attempt to more comprehensively understand the complexity of four YD proteins and to gain more insight into the novel functions they may accomplish in the neurons, we summarized the YD protein's networks, systematically searched and reviewed the YD genetic variants associated with neurodevelopmental disorders and finally interrogated the model organism Drosophila melanogaster.

Using DSP technology allows rapid, patient-specific assessment of the transcriptome in TMAs by in situ hybridization in spatially defined molecular compartments. Here we show a small set of candidate genes that are associated with outcome in this ICI-treated cohort. By intersecting two non-adjacent cores of the same patient tissue sample, we have begun to dissect tumor heterogeneity and pilot biomarker candidate information with unique molecularly defined compartments for tumor cells, lymphocytes, and macrophages.

Prognosis for the treatment of early stage STS remains difficult. Genomic alterations in this set of tumors was similar to previous reports of the genomic landscape in advanced STS. Transcriptomic analysis suggests that expression biomarkers may be useful in predicting recurrence following surgical resection of STS.

Furthermore, YEATS4 defects were associated with abnormal upregulation of bivalent embryonic stem cell genes, as previously shown in mice. Our work describes a potential mechanism of tumorigenesis-epigenetic instability caused by deficient H2A.Z deposition-and suggests that ULs arise through an aberrant differentiation program driven by deranged chromatin, emanating from a small number of mutually exclusive driver mutations.