Martin Teichmann, Team 07 – Targeting Transcription in Breast Cancer, invites Pr. Tapas Kundu to present a seminar.

Pr Tapas Kundu

Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) – India

Chromatin meets autophagy: A tale of nonhistone chromatin protein mediated genome organization and transcription regulation

The eukaryotic genome is intricately organized on a beads-on-string structure into nucleoprotein filaments. These filamentous structures consist of nucleosome beads, composed of approximately 147 base pairs of DNA and four octameric core histones. The folding pattern of these nucleosomes varies depending on the cellular state, ensuring the overall stability and balance within the organism. In addition to DNA and histones, various non-histone chromatin-associated proteins along with RNA molecules also play crucial roles in fine-tuning the organization and function of the genome. Our laboratory discovered that a highly abundant nuclear protein, human transcription coactivator PC4, is a non-histone component involved in the genome organization, stability, and maintenance of the epigenetic state. By employing atomic force and electron microscopy, we have demonstrated that PC4 directly interacts with core histones and linker histone H1 thus compacting the genome very efficiently. Our experimental results obtained from ATAC-Seq and RNA-Seq analysis provide valuable insights into the regulatory role of PC4 in genome organization. We observed that when PC4 is absent, there is a significant increase in genome decompaction accompanied by hyper-acetylation levels and abnormal gene expression patterns. Interestingly, we discovered that embryonic development was impaired in mice lacking PC4, indicating its essential role for survival. However, intriguingly, cell lines with reduced levels of PC4 exhibited enhanced cell proliferation rates and demonstrated resistance to radiation exposure. Further investigation revealed that the mechanism behind this radiation resistance involves the upregulation of autophagy pathways upon depletion of PC4. Remarkably, our ATAC-Seq data unveiled pervasive genomic decompaction coupled with heightened acetylation specifically at multiple loci related to autophagy-associated genes within these knockdown cells. A similar occurrence was observed in both brain and spleen-specific knockout models of PC4 in mice as well as C. elegans. However, it is worth noting that the brain-specific knockout of PC4 did not exhibit a pronounced phenotype apart from noticeable impairments in memory extinction. Interestingly, when PC4 was absent, there was a significant increase in the expression level of another non-histone protein that interacts with PC4. We intend to further investigate the primary role of this complex involving PC4 in heterochromatinization and its subsequent physiological functions.

📌 BBS conference room, 2 rue Dr Hoffamnn Martinot – Bordeaux

📆 10/09/2024, 9h30

Biography

Professor
Sir J. C. Bose National Fellow Silver Jubilee Professor (2015-16) Transcription and Disease Laboratory Molecular Biology and Genetics Unit JNCASR, Jakkur P.O., Bangalore -560064, India Ph: 91-80-2208 2679 / 2840/ 41, Mobile: 09449456334. Email: tapas@jncasr.ac.in

Former Director
CSIR- Central Drug Research Institute, Lucknow

Adjunct Professor,
Special Centre for Molecular Medicine,
Jawaharlal Nehru University, New Delhi

Lifetime Distinguished Professor
University of Mysore, Karnataka

Distinguished Visiting Professor
SDU Academy of Higher Education and Research,
Karnataka, India

Distinguished Visiting Professor
Indian Institute of Technology, Bombay

Prof. Tapas Kumar Kundu completed his master’s degree in Biochemistry from the University of Agricultural Sciences, Bangalore in 1989, winning a gold medal for standing first in the master’s degree examination. He was awarded his Ph.D. from the Indian Institute of Science, Bangalore, in the year 1995 with the best thesis award. Following his Ph.D., he had a short stint as a visiting foreign research associate in the National Institute of Genetics, Mishima, Japan, followed by a post-doctoral fellowship at the Rockefeller University, USA (1996-99). He joined JNCASR as in 1999. Prof. Kundu has made significant contributions in the area of regulation of gene expression and its link to disease and therapeutics. He is not only elucidating the mechanisms of transcription regulation through the epigenetic modifications but also targeting them to design new generation diagnostics, as well as therapeutics. Over the years, he has published several research papers in many international journals. Several patent applications from the laboratory have been granted and some are under process, which include several academically important research reagents with potential commercial values, some of which have already been commercialized by renowned companies. He is a fellow of four major national academies of India and served as an editorial board member of the Journal of Biological Chemistry (JBC) from 2011-2016. Presently, he is serving as an “Associate Editor” of the Journal of Biochemistry (Oxford University Press), Series Editor of Subcellular Biochemistry (Springer Nature), and the reviewing Editor of eLife Journal. As a Director of CSIR-CDRI, Lucknow, Prof. Kundu initiated many relevant academic and drug development programs. Under his leadership, several drug molecules reached Phase-I clinical trials and could be licensed to industries for further development. He also led and completed Phase-III clinical trials for anti-Covid 19 therapy which is awaiting DCGI approval. He was instrumental to establish the ‘Asian Forum for Chromatin and Chromosome Biology and ‘Chemical Biology Society, India’. Besides fundamental research, Prof. Kundu is also involved in teaching and organizing science outreach programs. His popular lectures on ‘Genes, Disease and Therapeutics’ have benefitted high school and college students greatly.

He is the recipient of several awards, noteworthy among which are: the Shanti Swarup Bhatnagar Prize from CSIR (2005), the National Academy of Science, India- Reliance Industries Platinum Jubilee Award (2008), the Sir JC Bose National Fellowship from DST (2010), the GD Birla award for scientific research (2011), The Ranbaxy Research Award 2011 in the field of Medical Sciences – Basic Research and India Innovation Award 2012 given by Merck Millipore 2012 (First place), Shri Om Prakash Bhasin Award for the year 2019 in the field of Health Medical Sciences by the Shri Om Prakash Bhasin Foundation, New Delhi, Sir M. Visvesvaraya Lifetime Achievement Award for Senior Scientists / Engineers (2021), and ICBS-2022 Global Lectureship Award by International Chemical Biology Society (ICBS).