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The mechanism by which cohesin controls gene expression

Objective

How cells retain, lose, and regain developmental plasticity is poorly understood due to ignorance of the molecular mechanisms regulating gene expression. Each gene is regulated by a unique set of factors and as a consequence the trans-acting factors and cis-acting chromatin modification states regulating a given gene are extremely rare. Transcription is affected by events taking place many thousands of base pairs away from the start, a property enabling developmental and evolutionary plasticity, presumably made possible by DNA looping or translocation of factors along chromatin. Most factors regulating a given gene function at many other genes, complicating interpretation of the consequences of altering the activity of such factors. It is difficult to exclude the possibility that phenotypes are knock-on effects. This could be surmounted if it were possible to observe individual genes in real time in three-dimensional space and to analyse the immediate consequences of altering the activity of regulatory factors. Of these, those capable of inter-connecting DNAs or of translocating large distances along chromatin are of interest. Cohesin is such a factor, composed of three core subunits, a pair of Smc proteins and a kleisin subunit, that interact with each other to form a huge tripartite ring, within which it is thought chromatin fibres are entrapped. In proliferating cells, cohesin’s primary function is to connect sister chromatids during DNA replication until the onset of anaphase, possibly by virtue of co-entrapment within a single ring. However, cohesin is present in most quiescent cells and it is becoming clear that it also regulates gene expression and recombination. This proposal has two goals: To image gene expression on polytene chromosomes and to investigate cohesin’s role during ecdysone-induced transcription. The advantage of this system is that we can use micro-injection of TEV protease to inactivate cohesin. A second goal is to develop the TEV system to

Field of science

  • /natural sciences/biological sciences/genetics and heredity/dna

Call for proposal

ERC-2011-ADG_20110310
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
Address
Wellington Square University Offices
OX1 2JD Oxford
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 2 421 212
Principal investigator
Kim Ashley Nasmyth (Prof.)
Administrative Contact
Gill Wells (Ms.)

Beneficiaries (1)

THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
EU contribution
€ 2 421 212
Address
Wellington Square University Offices
OX1 2JD Oxford
Activity type
Higher or Secondary Education Establishments
Principal investigator
Kim Ashley Nasmyth (Prof.)
Administrative Contact
Gill Wells (Ms.)