Transcriptional changes associated with Crebbp deletion are not associated with gene-proximal H3K18Ac changes. (A) Gene expression profiling was performed on purified B cells from adult disease-free mice to determine early molecular alterations associated with disease etiology. Differential gene expression analysis revealed a signature of genes with significantly (false discovery rate < 0.25, fold change >1.2) reduced or increased expression associated with deletion of 1 or both alleles of Crebbp in the EµBcl2 background. This represents the intersection of head-to-head comparisons between mice with both alleles of Crebbp intact (Cbp^F/FxEµBcl2) compared with those with either 1 allele (Cbp^WT/ΔxEµBcl2) or 2 alleles (Cbp^Δ/ΔxEµBcl2) of Crebbp deleted and included increased expression of the Myc oncogene. The samples for which ChIP-seq was also performed are annotated at the bottom of the figure with roman numerals. (B) Increased expression of Myc was confirmed by immunohistochemical staining of spleens from Cbp^Δ/ΔxEuBcl2 mice compared with an age-matched control (Cbp^F/F). (C) Heat maps show the level of H3K18Ac from 10 kb upstream to 10 kb downstream from the TSS of genes with differential expression associated with Crebbp deletion. ChIP-seq was performed on the same samples that were interrogated by gene expression profiling, as annotated by corresponding roman numerals in panels A and C. The H3K18Ac level of each gene is aligned with the expression levels in panel A, and the average signal (line) ± the standard deviation (shaded region) is summarized for genes with reduced (blue) or increased (red) gene expression at the top of the heat map. There is a peak of H3K18Ac at the TSS of most genes with differential expression, showing our ability to detect H3K18Ac at TSSs. However, the changes in gene expression between strains were not associated with changes in H3K18Ac at the TSS ± 10 kb.