The document describes a feed-forward loop (FFL) network motif. An FFL consists of two input transcription factors where one regulates the other and they jointly regulate a third gene. FFLs can have coherent or incoherent logic and either AND or OR logic. The document then discusses the structure and functions of FFLs, including how they can filter signals and respond to persistent stimuli. It also describes developing a database of FFLs to analyze regulatory networks.

1. BACA THEODOR-STEFAN and SINIAVSCHI RADU
MASTER ITEMS 2012
FEED-FORWARD LOOP
CENTRAL DATABASE
Based on the article: STRUCTURE AND FUNCTION OF THE
FEED-FORWARD LOOP NETWORK MOTIF by S. Mangan and U. Alon

2. What is a FEED-FORWARD LOOP?
Feed-forward loop (FFL) is a motif,
consisting in a three-gene pattern
composed of two input transcription
factors. Each of the three interactions in
the FFL can be either activating or
repressing (coherent or incoherent).
Simple
regulation
of Z by X
and Y.
Transcription factor X regulates transcription factor
Y, and both jointly regulate Z. Sx and Sy are the
inducers of X and Y, respectively. The action of X
and Y is integrated at the Z promoter with a cis-
regulatory input function , such as AND or OR logic.

3. FFL- Structure
E. coli example:

4. COHERENT and INCOHERENT FFL type
•
Decide from fluctuating signal
•
Filter out pulses
•
Respond to persistent stimulations
•
Rapidly shut down
•
Easly reverse
•
Initially reacts strongly
•
Later comes back to intermediate
levels

5. FFL- Structure
Logic function
 AND logic
 OR logic
X and Y respond to
external stimuli

6. Coherent Type-1 FFL – AND logic
 Sx appear, X rapidly changes to X*
 X* binds to gene Z, but cannot activate it
 X* binds to gene Y, and begins to transcript it
 Z begins to be expressed after Ton time, when Y* crosses the
activation threshold Kyz

7. Incoherent Type-1 FFL

8. MATERIALS AND METHODS
Equations for
Gene Regulation Reactions

9. MATERIALS AND METHODS
Parameters for Functional FFLs

10. RESULTS

11. RESULTS

12. RESULTS

13. RESULTS

14. The FFL Database
An user-friendly web app that integrates feed forward loops so scientists and other
enthusiasts could use the results for educational and scientifical purposes.

15. The FFL Database
An user-friendly web app that integrates feed forward loops so scientists and other
enthusiasts could use the results for educational and scientifical purposes.

16. The actual FFL Database

17. Methods of FFL Database
 Search where we can get information about the regulatory networks
 Get from the information about the regulation by Transcription Factors.
 Construct an algorithm to extract the FFL motives different organisms
regulatory networks.
 Make a hierarchical clasiffication of FFLs elements.
 Make a clasiffication acording to the origin of the signal that TFs sense.
 Search for differences betwen the data on each position of the FFLs
making statistical tests to validate significance.

18. CONCLUSIONS
 Incoherent FFLs – sign-sensitive accelerators.
 Coherent FFLs – sign-sensitive delays.
 Some FFL occur more often than the others.
 Observe how TFs that detect different-origin signals compose
 Observe the dinamics on the TRN looking for the formation of specific
topological structure, FFL
 Search for significative differences on the data by statistical tests on
each position of the FFLs.

19. Thank you
for your attention!