Differential Histone 3 Lysine 56 Acetylation in hESC and Somatic Cells.

All the cells in our body, each and every one of them, came from a single cell!! What makes a single cell form so many different body cells that can carry out variety of specialized functions? The capacity of self renewal and differentiation are the two characteristic potentials of Human Embryonic Stem Cell (hESC). All stem cells have the ability to self-renew and the ability to differentiate. Embryonic stem cells are unique in that they are derived from the inner cell mass of the developing blastocyst and, thus, can give rise to all the tissue types of the embryo. Mammalian development requires the specification of over 200 unique cell types from a single totipotent cell. Histones are intimately associated with DNA and are highly conserved proteins. Variety of post-translational modification, amino acid sequences and their three dimensional structures are highly conserved. These modifications can be acetylation, methylation, phosphorylation, ubiquitination, polyribosylation of specific histone residues.
Approximately 1% of histone 3 is acetylated in human cells. Acetylated lysines are recognised by bromodomains of ATPase remodelling complex to promote transcription. Lysine 56 acetylation (K56Ac) in the helical core of H3 differentiates between epigenetic state of pluripotent and somatic cells. The K56Ac targets are gene specific like canonical histone genes which are bound by transcription factors of hESC NANOG, SOX2 and OCT4. Differential K56Ac is observed in human embryonic stem cell and somatic cells. GO analysis revealed that the genes involved in signal transduction, tissue remodelling and organ development show K56Ac in somatic cells. K56Ac relocates during transition from pluripotent cell to differentiated state. Transcript levels of transcription factors NANOG, SOX2 and OCT4 drop drastically in lineage committed cells. The most deacetylated loci that were observed in differentiated cell are the hESC specific miRNA gene grp mir302 which plays a critical role in development and regulation of ESCs, HOX genes on the other hand are most acetylated. K56Ac is observed to be depleted in canonical histone genes (H1, H2A, H2B, H4 & H5) in somatic cells. K56Ac spatial patterns are parallel to spatial binding of NSO proteins and are linked to hESC core transcriptional network. K56Ac marks both active and inactive genes. By marking core transcriptional network of hESC K56Ac can predict new NSO transcriptional regulator targets can be identified

Jayee Patil
41912094