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 transcript ion factors have been identified as histone acetyltransferases. In add ition, retinoblastoma protein and some co-factors can form a complex w ith histone deacetylases. These discoveries provide direct evidence th at modification of chromatin structure is crucial for gene activation. However, the role of chromatin structure in cardiac-specific expressi on has not yet been elucidated, The potential significance of chromati n structure in cardiac-specific gene expression is indicated by: (1) h eterogeneous human SWI/SNF chromatin remodelling factors among various tissues: (2) several chromatin remodelling factors shown to be expres sed preferentially in the heart; (3) the demonstration of chromatin re modelling of the cardiac beta-myosin heavy chain gene (MyHC) during ca rdiac development. We therefore propose to study cardiac-specific chro matin remodelling activity in order to elucidate mechanisms controllin g the reactivation of the fetal heart genetic program in the hypertrop hic heart. (C) 1998 Academic Press