Principles of Dynamic gene regulation in mammals, hosted by Sarah Teichmann

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• Ido Amit, Weizman Institute, Israel
• Friday 19 October 2012, 14:30-15:30
• CIMR (Cambridge Institute for Medical Research), Sackler Lecture Theater on level 7.

If you have a question about this talk, please contact Dr Tennie Videler.

Dynamic binding of transcription factors to DNA elements specifies gene expression and cell fate, in both normal physiology and disease. To date, our understanding of mammalian gene regulation has been hampered by the difficulty of directly measuring in vivo binding of large numbers of transcription factors to DNA . Here, we develop a high-throughput indexed Chromatin ImmunoPrecipitation (iChIP) method coupled to massively parallel sequencing to systematically map protein-DNA interactions. We apply iChIP to reconstruct the physical regulatory landscape of a mammalian cell, by building genome-wide binding maps for 41 transcription factors (TFs) and chromatin marks at four time points following stimulation of primary dendritic cells (DCs) with pathogen components. Using over 200,000 TF-DNA interactions in these maps, we derive the first comprehensive and dynamic physical model of a regulatory network in a mammalian cell. Our data demonstrate that transcription factors vary substantially in their binding dynamics, genomic localization, number of binding events, and degree of interaction with other factors. Further, many of the TFs-DNA interactions are pre-established prior to stimulation and maintained in a poised state, specifically on immediate early genes. We show, that the network is composed of three distinct spatial-temporal regulatory layers: Pioneers define the epigenetic state during cellular differentiation, Primers prime, and Transducers mediate the transcription of genes upon stimulation. These factors determine the magnitude and timing of stimulus induced gene expression. By integrating these TF binding maps with RNAi perturbations, we identify two distinct regulatory schemes controlling the response. “Inflammatory” genes are controlled by a modular and redundant regulatory program (OR gate), whereas “anti-viral” response genes are controlled by an all-or-none response (AND gate). Together, these principles highlight how mammalian cells organize transcriptional networks

This talk is part of the Cambridge Immunology series.

This talk is included in these lists:

• CIMR (Cambridge Institute for Medical Research), Sackler Lecture Theater on level 7
• Cambridge Infectious Diseases
• Pathology Seminars

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