Meeting Abstract
S1.1-2 Saturday, Jan. 4 08:30 Epigenetic Mechanisms and Environmental Signals SOLIMAN, Karam F; Florida A&M University karam.soliman@famu.edu
Exposure to specific environmental conditions can alter the epigenome, as the control mechanism of genomic DNA expression, and can lead to long-term phenotypic consequences as certain chronic diseases. These epigenetic changes are plastic and can be altered at different points of development, which can have varying impact on disease incidence. Epigenetic alterations such as DNA methylation or histone modifications patterns are associated with each unique maladaptive phenotype. This is further complicated by a limitless combination of environmental cues that could alter the epigenome. DNA methylation is initiated by DNMTs that methylate CpGs, which are tagged by MBD proteins attached to potent repression complexes. The repression complexes, in turn, control modifications to histones H3 and H4 tails, which perpetuate constriction and make stable modifications to the histone cores H2A and H2B to prevent histone unit ejection/nucleosomal displacement. These collective events are associated with stabilized tension of the histone H1 linker. HP1α and HP1β proteins tether silencing elements from methylated CpGs to ATPase remodeling machinery-together, in order to tightly crowd methylated DNA close to the nucleosomes, thereby blocking transcription elements. The positioning of silenced heterochromatin along the nuclear envelope is carried on by lamins. Within euchromatin, unmethylated CpG islands remain open to transcription initiation complexes by opposing processes such as hyperacetylation of histone tails, H2A core variant exchange, HMG proteins binding. In summary, research in this area indicates that the more we learn about epigenetic mechanisms of gene regulation, the more complex it seems. However, more understanding of the environmental role in the epigenetic basis of diseases will help in providing more effective means in disease prevention and to develop new improved therapies.(Supported by NIH grants G12 MD007582and P20 MD006738)
