Project description:Recent work from others and us revealed interactions between the Sin3/HDAC complex, the H3K4me3 demethylase KDM5A, GATAD1 and EMSY. Here, we characterize the EMSY/KDM5A/SIN3B complex in detail by quantitative interaction proteomics and ChIP-sequencing. We identify a novel substoichiometric interactor of the complex, ZNF131, which recruits EMSY to a large number of active, H3K4me3 marked promoters. Interestingly, using an EMSY knock-out line and subsequent rescue experiments, we show that EMSY is in most cases positively correlated with transcriptional activity of its target genes and stimulates cell proliferation. Finally, by immunohistochemical staining of primary breast tissue microarrays we find that EMSY/KDM5A/SIN3B complex subunits are frequently overexpressed in primary breast cancer cases in a correlative manner. Taken together, these data open venues for exploring the possibility that sporadic breast cancer patients with EMSY amplification might benefit from epigenetic combination therapy targeting both the KDM5A demethylase and histone deacetylases.
Project description:Genome-wide gene expression pattern of E47 KO versus WT HSCs from primary and secondary recipient mice were analysis using Agilent one-color micro-array analysis.
Project description:Genome-wide gene expression pattern of E47 KO versus WT HSCs from primary and secondary recipient mice were analysis using Agilent one-color micro-array analysis. Two replicates from 4 samples are analyzed. The sample from the WT mouse were set as their reference sample.
Project description:SYNCRIP depletion results in HSCs losing their self renewal abilities. Next generation sequencing was conducted in SYNCRIP WT and KO HSCs to investigate the transcriptional changes that occur, and result in the loss of self-renewal.