Vertebrate GAF/ThPOK: emerging functions in chromatin architecture and transcriptional regulation.

GAGA factor of Drosophila melanogaster (DmGAF) is a multifaceted transcription factor with diverse roles in chromatin regulation. Recently, ThPOK/c-Krox was identified as its vertebrate homologue (vGAF), which has a basic domain structure similar to DmGAF and is decorated with a number of post-translationally modified residues. In vertebrate genomes, vGAF associates with purine-rich GAGA sequences and performs diverse chromatin-mediated functions, viz., gene activation, repression and enhancer blocking. Expansion of regulatory chromatin proteins with the acquisition of PTMs appears to be the general trend that facilitated the evolution of complexity in vertebrates. Here, we compare the structural and functional features of vGAF with those of DmGAF and also assess the possible functional redundancy among paralogues of vGAF. We also discuss the underlying mechanisms which aid in the diverse and context-dependent functions of this protein.

Single Amino Acid Repeats in the Proteome World: Structural, Functional, and Evolutionary Insights.

Microsatellites or simple sequence repeats (SSR) are abundant, highly diverse stretches of short DNA repeats present in all genomes. Tandem mono/tri/hexanucleotide repeats in the coding regions contribute to single amino acids repeats (SAARs) in the proteome. While SSRs in the coding region always result in amino acid repeats, a majority of SAARs arise due to a combination of various codons representing the same amino acid and not as a consequence of SSR events. Certain amino acids are abundant in repeat regions indicating a positive selection pressure behind the accumulation of SAARs. By analysing 22 proteomes including the human proteome, we explored the functional and structural relationship of amino acid repeats in an evolutionary context. Only ~15% of repeats are present in any known functional domain, while ~74% of repeats are present in the disordered regions, suggesting that SAARs add to the functionality of proteins by providing flexibility, stability and act as linker elements between domains. Comparison of SAAR containing proteins across species reveals that while shorter repeats are conserved among orthologs, proteins with longer repeats, >15 amino acids, are unique to the respective organism. Lysine repeats are well conserved among orthologs with respect to their length and number of occurrences in a protein. Other amino acids such as glutamic acid, proline, serine and alanine repeats are generally conserved among the orthologs with varying repeat lengths. These findings suggest that SAARs have accumulated in the proteome under positive selection pressure and that they provide flexibility for optimal folding of functional/structural domains of proteins. The insights gained from our observations can help in effective designing and engineering of proteins with novel features.