Additional file 6: Table S4. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Expression in undifferentiated murine embryonic stem (ES) cells of genes that escape X chromosome inactivation (XCI) after differentiation (BC cell lines)

Additional file 11: Figure S5. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Chromosomal distribution of genes enriched in BCO when compared to BCF ES cells. BCO ES cell lines had enrichment of 423 genes, 49% of which overlapped with genes enriched in BCM relative to BCF (FDR < 0.01). The genes common to both BCO and BCM had statistically higher enrichment relative to BCF, averaging 2.55- versus 2.23-fold (students t-test, two tailed p < 0.001). Error bars denote standard deviation

Additional file 10: Table S6. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Genes with a sex-specific bias that overlap between ES cells and 5.5 dpc embryos

Additional file 9: Figure S4. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Comparison of expression differences for 14 selected genes from our dataset with a single-cell (sc) RNA-seq study [75] shows a high degree of correlation. Individual plots of expression from the scRNA-seq analysis shows the variability within the assay and the abundance of zero readouts for some genes. To avoid this confounder, a sign test was performed using a binomial exact test which affirmed the sex-specific biases seen within our dataset

Additional file 7: Table S5. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Examples of genes expressed in undifferentiated ES cells of genes that do not escape XCI (BC cell lines)

Additional file 1: Figure S1. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Derivation of mouse ES cell lines. F1 hybrid blastocysts were obtained at embryonic day 3.5 from reciprocal crosses of mouse substrains C57BL/6 and CAST/EIJ (designated as B and C, respectively). Blastocysts were cultured individually and used to establish independent cell lines

Additional file 8: Figure S3. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Allele-specific expression analysis for imprinted gene Cdkn1c. RT-PCR was followed by allele-specific restriction digest of the Cdkn1c coding sequence and polyacrylamide gel analysis. A single nucleotide polymorphism in the M. castaneus allele generates a restriction site for aTaqI. Two different F1 hybrid ES cell lines each derived from reciprocal crosses of C57BL/6 (B) and CAST/EIJ (C) mice exhibited monoallelic (BxC) and biased expression (CxB) from the maternal allele. The first lane is the marker, the last two lanes are digested controls from PCR products from B and C genomic DNA

Additional file 5: Figure S2. of Sex chromosomes drive gene expression and regulatory dimorphisms in mouse embryonic stem cells

Identification of candidate regulatory elements. (A) Top, graphic display of the conservation profiles for regions upstream of Zfx from Dcode.org [64, 110]. The base genome is mouse. Evolutionarily conserved regions (ECRs) of a minimum of 100 bp conserved above 70% sequence identity are displayed as red (intergenic) peaks, with the x-axis representing positions in the base genome and the y-axis representing percentage identity between the base and the aligned genomes. Predicted transcription factor motifs are depicted as colored bars. Arrowhead points to predicted motif of TF expressed more highly in female ES cells. Bottom, UCSC genome browser view of the same regions including histone modifications from ENCODE data in mouse ES cells ( http://genome.ucsc.edu , NCBI37/mm9). (B) Conservation analysis, TF motif prediction and UCSC browser view as in (A) for the Tcf3 gene. Arrowhead points to predicted motif of TF expressed more highly in male ES cells. (C) Conservation analysis, TF motif prediction and UCSC browser view as in (A) for the Apln gene, with arrowheads indicating motifs predicted to bind TFs more highly expressed in male ES cells

Differentially methylated genes and androgen receptor re-expression in small cell prostate carcinomas

<p>Small cell prostate carcinoma (SCPC) morphology is rare at initial diagnosis but often emerges during prostate cancer progression and portends a dismal prognosis. It does not express androgen receptor (AR) or respond to hormonal therapies. Clinically applicable markers for its early detection and treatment with effective chemotherapy are needed. Our studies in patient tumor–derived xenografts (PDX) revealed that AR–negative SCPC (AR⁻SCPC) expresses neural development genes instead of the prostate luminal epithelial genes characteristic of AR–positive castration-resistant adenocarcinomas (AR⁺ADENO). We hypothesized that the differences in cellular lineage programs are reflected in distinct epigenetic profiles. To address this hypothesis, we compared the DNA methylation profiles of AR⁻ and AR⁺ PDX using methylated CpG island amplification and microarray (MCAM) analysis and identified a set of differentially methylated promoters, validated in PDX and corresponding donor patient samples. We used the Illumina 450K platform to examine additional regions of the genome and the correlation between the DNA methylation profiles of the PDX and their corresponding patient tumors. Struck by the low frequency of AR promoter methylation in the AR⁻SCPC, we investigated this region's specific histone modification patterns by chromatin immunoprecipitation. We found that the AR promoter was enriched in silencing histone modifications (H3K27me3 and H3K9me2) and that EZH2 inhibition with 3-deazaneplanocin A (DZNep) resulted in AR expression and growth inhibition in AR⁻SCPC cell lines. We conclude that the epigenome of AR⁻ is distinct from that of AR⁺ castration-resistant prostate carcinomas, and that the AR⁻ phenotype can be reversed with epigenetic drugs.</p

Additional file 2: Table S4. of Epigenetic synergy between decitabine and platinum derivatives

Primers for bisulfite pyrosequencing.Table S5. Primers for ChIP Q-PCR