The third Dimension of gene regulation: it’s all in the looping!

Sanjeev Galande
National Centre for Cell Science

Non-random and compartmentalized distribution of functional components is a hallmark of the nucleus in multicellular organisms. In these organisms, DNA is organized with help of basic proteins into an orderly packaged compact structure called chromatin. Out of the thousands of protein-coding ‘genes’ or DNA segments that each cell contains, only a fraction is used at any given time, and those genes that are seldomly used are packaged much tightly as compared to the ones that are ‘expressed’ or used during the lifetime of a cell. Moreover, the various hierarchical states of the packaging are interconvertible depending upon the physiological need of the cell and also contribute in variety of ways to achieve stringent regulation of gene activity (Spector, 2003). Dynamic nature of chromatin loops is one such mechanism wherein the structural transitions lead to functional consequences. Technological advances in recent years have provided unprecedented insights into the role of chromatin organization and interactions of various structural-functional components towards gene regulation. The global chromatin organizer SATB1 has emerged as a key factor integrating higher-order chromatin architecture with gene regulation (Galande et al., 2007). Studies in recent years have unraveled the role of SATB1 in organization of chromatin “loopscape” and its dynamic nature in response to physiological stimuli (Kumar et al., 2007). At genome-wide level, SATB1 seems to play a role in organization of the ‘transcriptionally poised’ chromatin, the part of chromatin that contains genes that are required for execution of specific cellular processes. The implications of these findings towards development and differentiation of the cells of the immune system will be discussed.

References:

1. Spector DL. The dynamics of chromosome organization and gene regulation. Annu Rev Biochem. 2003; 72:573-608.

2. Galande S, Purbey PK, Notani D, Kumar PP. The third dimension of gene regulation: organization of dynamic chromatin loopscape by SATB1. Curr Opin Genet Dev. 2007; 17:408-14.

3. Kumar PP, Bischof O, Purbey PK, Notani D, Urlaub H, Dejean A, Galande S. Functional interaction between PML and SATB1 regulates chromatin-loop architecture and transcription of the MHC class I locus. Nat Cell Biol. 2007; 9:45-56.

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