SOURCE-LINKED INTELLIGENCE

Looping Enhancers and Promoters give Specificity

CORDIS · observation · Publication date unknown

enome regulation. The factors involved and sequence-level determinants of enhancer-promoter (E-P) specificity remain elusive. Here, we will combine systematic genetics, high-resolution genomics, and deep learning to perform the first large-scale functional dissection of the trans-factors and cis-regulatory features required for E-P looping and specificity in an in vivo context, using Drosophila embryogenesis. Drosophila has a track record of identifying conserved regulators of E-P communication from flies to man, including the discovery of Ldb1 and cohesin, and offers unmatched resources for this task: (a) genome-wide lines enabling tissue-specific knockdown of every gene; (b) efficient P-element transposon hopping, to force loops and sense enhancers to assess E-P specificity; (c) a near-complete map of regulatory elements for all embryonic stages. This proposal has three complementary Aims, to: 1) Identify new genes and cis-regulatory features functionally required for E-P looping; 2) Dissect, model, and predict sequence rules underlying E-P specificity & 3) Determine functional E-

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recordType

award

status

SIGNED

region

EU

value

2499626

unit

EUR