Research

Madhulika Srivastava

M. Sc.
Jawaharlal Nehru University, New Delhi

Ph. D.
Jawaharlal Nehru University, New Delhi

Postdoctoral Research
NICHD, NIH, USA

Email
madhu@nii.ac.in

 

Research Interest

Epigenetics, chromatin organization, Mammalian gene regulation

Group Members

Manisha Jalan, Abhilasha Kanaujia, Faizan Uddin, Ramesh Yadav and Bhan Singh

Summary of Research

Chromatin organization plays a crucial role in determining the specificity of transcription by modulating the accessibility of transcription factors to the specific sequences in DNA.

The epigenetic regulation, involving heritable but reversible alterations of the chromatin structure, organization and function, thus becomes crucially important for the establishment and maintenance of expression profiles in the cell. Our interest is in understanding some of the basic aspects pertaining to the role of chromatin organization in mammalian gene regulation.

We are particularly interested in understanding of the mechanisms by which cis-acting regulatory elements interact with each other in context of chromatin. Such interactions are crucial for appropriate regulation of nuclear processes like transcription and VDJ recombination. In this context, CTCF dependent insulators play an important role in the functional organization of the mammalian genome as they can coordinate intrachromosomal and interchromosomal contacts and thus influence cis-DNA interactions.  Insulators have been identified from diverse metazoan species and global analysis has recently predicted the presence of several thousand sites in the human genome that could potentially act as insulators aiding in specific regulation of genes. However, the mechanisms by which the insulators organize functionally distinct domains and restrict the enhancer activity to specific promoters remain only partially understood. The current efforts in the lab focus on understanding different aspects of the mechanisms by which mammalian insulators influence chromatin domain organization and contribute to regulation of nuclear processes.

Selected Publications

  • 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 andSrivastava 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.
  • Srivastava M, Frolova E, Rottinghaus B, Boe S, Grinberg A, Lee E, Love PE, Pfeifer K(2003) Imprint control element mediated secondary methylation imprints at the Igf2/H19 locus Journal for Biological Chemistry 278: 5977-5983
  • Kaffer CR, Srivastava M, ParkKye-Yoon, Ives E, Hsieh S, Batlle J, Grinberg A, Huang SP, and Pfeifer K (2000) A transcriptional insulator at the imprinted H19/Igf2 locus Genes and Development 14: 1908-1919.
  • Srivastava M, Hsieh S, Grinberg A, William Simons L, Huang SP, Pfeifer K (2000) H19 and Igf2 monoallelic expression is regulated in two distinct ways by a shared cis acting region upstream of H19 Genes and Development 14: 1186-1195.

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