One of the mysteries in Biology, not yet fully understood, is the process of cell differentiation. For instance, bone marrow stem cells continuously replenish all blood cells throughout life. Consistently, when bone marrow from a healthy individual is infused into a patient, stem cells reach bone marrow and eventually self-renew and reconstitute an entirely new immune system comprising lymphoid and myeloid lineages. However, the molecular mechanisms that dictate cell fate choice remain poorly understood. Recent studies, published in Nucleic Acids Research (2017), from Pongubala’s laboratory at University of Hyderabad, demonstrate that chromatin undergoes extensive reorganization as the progenitor cell transit into a committed B cell stage, indicating that cell fate choice is governed by cell type-specific chromatin regulatory network.
Reporting in Nucleic Acids Research (2017), studies from Prof. Jagan Pongubala’s laboratory of the Department of Animal Biology, School of Life Sciences, University of Hyderabad at University of Hyderabad (UoH), demonstrate that chromatin undergoes reorganization as progenitor cell transit into a committed B cell stage. These studies carried out along with research scholars B. Ravi and Anurupa Devi reveal that chromatin is organized into active and inactive compartments, and during differentiation a distinct subset of genomic loci switch between these compartments.
These studies reveal that genome is partitioned into active and inactive compartments and a subset of genomic loci switch between these regions; thereby genes are correspondingly regulated, during the developmental transition. Additionally, these studies demonstrate that genome within these compartments is organized as subdomains that are highly self-interactive in nature. A substantial number of subdomains are dynamic and undergo structural alterations as a result of changes in chromatin interactions. Changes in chromatin interactions are closely associated with alterations in cellular gene expression pattern. Taken together, these studies demonstrate that alterations in genome architecture dictate gene expression pattern and that controls the process of cellular differentiation. However, many questions remain about how many of these chromatin interactions are functionally important and how those interactions are initiated and maintained to sustain lineage identity and functional state of a cell. A better understanding of the combinatorial interactions of the regulatory elements and the factors that bind to those sequences may eventually lead to better therapeutic strategies for treatment of genetic diseases as well as developmental disorders including cancer.
Nucleic Acids Research ( NAR ) is a prestigious journal that publishes the results of leading edge research into physical, chemical, biochemical and biological aspects of nucleic acids and proteins involved in nucleic acid metabolism and/or interactions. In 2016 as per the Journal Citation Reports, published annually as part of the Science Citation Index by ISI, NAR has an Impact Factor of 10.162.