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SUMMARY:Integrating analog and digital modes of gene expression - Martin  
 Howard (John Innes Centre\, Norwich)
DTSTART:20231016T133000Z
DTEND:20231016T143000Z
UID:TALK206071@talks.cam.ac.uk
DESCRIPTION:Quantitative gene regulation at the population level can be ac
 hieved by two fundamentally different modes of regulation at individual ge
 ne copies. A &ldquo\;digital&rdquo\; mode involves binary ON/OFF expressio
 n states\, with population level variation arising from the proportion of 
 gene copies in each state\, while an &ldquo\;analog&rdquo\; mode involves 
 graded expression levels at each gene copy. At the Arabidopsis floral repr
 essor FLOWERING LOCUS C (FLC)\, &ldquo\;digital&rdquo\; Polycomb silencing
  is known to facilitate quantitative epigenetic memory in response to cold
 . However\, whether FLC regulation before cold involves analog or digital 
 modes is unknown. Using quantitative fluorescent imaging of FLC mRNA and p
 rotein\, together with mathematical modelling\, we find that FLC expressio
 n before cold is regulated by both analog and digital modes. We demonstrat
 e a temporal separation between the two modes\, with analog preceding digi
 tal. The analog mode can maintain intermediate expression levels at indivi
 dual FLC gene copies\, allowing subsequent digital silencing\, where these
  copies switch OFF stochastically and heritably without cold. The timescal
 e of this one-way switch is governed by the strength of transcription: hig
 h transcription prevents switching\, while low levels of transcription all
 ow for rapid switching. In this way\, analog and digital regulation are co
 mbined: analog regulation precedes digital with a time delay for the switc
 h depending on the strength of transcription. Overall\, our data present a
  new paradigm for gradual repression\, elucidating how analog transcriptio
 nal and digital epigenetic memory pathways can be integrated.
LOCATION:Seminar Room 2\, Newton Institute
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