Profile
Nuclear processes depend on interactions between cis acting regulatory elements and trans-acting factors and are intricately regulated by chromatin structure and organization. The dynamism of these interactions and the mechanistic diversity by which they are regulated is intriguingly complex and aberrations in chromatin organization lead to developmental disorders as well as metabolic diseases. Appropriate higher order chromatin organization is also necessary for generating RAG mediated VDJ recombination at Antigen receptor loci to generate a vast and diverse repertoire of functional genes encoding immunoglobulin and T cell receptors. Antigen receptor loci, therefore serve as useful models to understand the interdependence of chromatin organization and gene regulation. We are investigating the chromatin organization and regulation of transcription and VDJ recombination at murine TCRb locus.
Current Focus Areas
CTCF, a DNA binding protein with multifunctional attributes, is an important contributor to chromatin organization. It has thousands of binding sites in mammalian genomes. We are investigating various aspects of chromatin organization as influenced by CTCF using wild type and genetically manipulated TCRb loci.
Enhancers are the vanguards of tissue specific gene regulation. While they are well established to be critical regulators of chromatin accessibility at antigen receptor loci, their role in large-scale chromosomal reorganization within the nucleus is relatively less explored and is being investigated.
Selected Publications
Yadav M, Jalan M, Srivastava M (2022) Enhancer dependent repositioning of TCRb locus with respect to the chromosome territory. Journal of Molecular Biology, volume 434(7):167509 doi: 10.1016/j.jmb.2022.167509
Rawat P, Jalan M, Sadhu A, Kanaujia A, Srivastava M (2017) Chromatin Domain Organization of TCRb locus and its perturbation by ectopic CTCF binding. Molecular and Cellular Biology, 37, Issue 9, e00557-16
Varma G, Rawat P, Jalan M, Vinayak M, Srivastava M (2015) Influence of a CTCF dependent insulator on multiple aspects of enhancer mediated chromatin organization. Molecular and Cellular Biology, 35, 3504-3516
Shrimali S, Srivastava S, Varma G, Grinberg A, Pfeifer K and Srivastava M (2012) An ectopic CTCF dependent transcriptional insulator influences the choice of Vb gene segments for VDJ recombination at TCRb locus. Nucleic Acids Research 40: 7753-7765.
Singh V and Srivastava M (2008) Enhancer blocking activity of the insulator at H19- ICR is independent of chromatin barrier establishment. Molecular and Cellular Biology 28: 3767-3775.