Chromatin Structure and Cardiac Gene Expression

Gene activation is often preceded by or accompanied by a perturbation of the chromatin structure. Recently, several co-factors of transcription factors have been identified as histone acetyltransferases. In addition, retinoblastoma protein and some co-factors can form a complex with histone deacetylases. These discoveries provide direct evidence that modification of chromatin structure is crucial for gene activation. However, the role of chromatin structure in cardiac-specific expression has not yet been elucidated. The potential significance of chromatin structure in cardiac-specific gene expression is indicated by: (1) heterogeneous human SWI/SNF chromatin remodelling factors among various tissues; (2) several chromatin remodelling factors shown to be expressed preferentially in the heart; (3) the demonstration of chromatin remodelling of the cardiacβ-myosin heavy chain gene (MyHC) during cardiac development. We therefore propose to study cardiac-specific chromatin remodelling activity in order to elucidate mechanisms controlling the reactivation of the fetal heart genetic program in the hypertrophic heart.