Description
We found that the bone marrow microenvironment of Crebbp+/- mice was unable to properly maintain the immature stem - and progenitor pools. Instead, it stimulates myeloid differentiation that progresses into a myeloproliferative-like disease. Since CREBBP is a transcriptional co-activator, we used gene expression analysis to globally assess functional deficiencies in Crebbp+/- bone marrow stroma cells at a molecular level. Ep300 encodes a protein which is highly similar in structure and function to CREBBP; nevertheless, Ep300+/- mice suffer neither excessive myeloid differentiation nor loss of HSCs. Therefore, to identify expression changes specifically related to Crebbp heterozygosity, we focused on genes that showed significant differences in expression levels between Crebbp+/- and wild-type bone marrow stroma but no difference between Ep300+/- and wild-type.