Transcription of insulin is regulated by the binding of various transcription factors to the ~400 base pairs before the insulin transcription start site, called the "insulin regulatory sequence".[1] This sequence is made up of several distinct regions with different biochemical properties, each of which serve as binding sites for distinct regulatory proteins. First, multiple A/T-rich sequences, called "A elements", each of which contains a "TAAT" reocognized by homeodomain proteins. These regions are primarily bound by PDX-1, but also Cdx2 and Isl-1.[1] Second, two so-called "C elements" – C1 located 107–118 base pairs before the transcription start site; C2 311–317 base pairs before the start site. C1 is bound by RIPE3b1 via MafA. C2 (also called the "pancreatic islet cell enhancer sequence" or "PISCES") is bound by PAX6.[1] Third, an "E element" (two in rodents) with sequence GCCATCTG is 91–100 base pairs before the transcription start site and binds the helix-loop-helix transcription factors NEUROD1.[1] Lastly, several "cyclic AMP response elements" with sequence TGACGTCA that binds CREB.[1]
In humans, a "Z-element" resides 243–292 base pairs before the start site and binds a complex called ZaI, as well as PDX-1 and MafA.[1]
| Regulatory sequence | binding transcription factors |
|---|---|
| ILPR | Par1 |
| A5 | Pdx1 |
| negative regulatory element (NRE)[3] | glucocorticoid receptor, Oct1 |
| Z (overlapping NRE and C2) | ISF |
| C2 | Pax4, MafA(?) |
| E2 | USF1/USF2 |
| A3 | Pdx1 |
| CREB RE | CREB, CREM |
| A2 | – |
| CAAT enhancer binding (CEB) (partly overlapping A2 and C1) | – |
| C1 | – |
| E1 | E2A, NeuroD1, HEB |
| A1 | Pdx1 |
| G1 | – |
References
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