EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation.
EID1 (E1A-like inhibitor of differentiation 1) functions as an inhibitor of nuclear receptor-dependent gene transcription by directly binding to co-regulators. Alternative targets include the co-repressor small heterodimer partner (SHP, NR0B2) and the co-activators CBP/p300, indicating that EID1 utilizes different inhibitory strategies. Recently, EID2 was characterized as an inhibitor of muscle differentiation and as an antagonist of both CBP/p300 and HDACs. Here, we describe a third family member designated EID3 that is highly expressed in testis and shows homology to a region of EID1 implicated in binding to CBP/p300. We demonstrate that EID3 acts as a potent inhibitor of nuclear receptor transcriptional activity by a mechanism that is independent of direct interactions with nuclear receptors, including SHP. Furthermore, EID3 directly binds to and blocks the SRC-1 interacting domain of CBP, which has been implicated to act as the interaction surface for nuclear receptor co-activators. Consistent with this idea, EID3 prevents recruitment of CBP to a natural nuclear receptor-regulated promoter. Our study suggests that EID-family members EID3 and EID1 act as inhibitors of CBP/p300-dependent transcription in a tissue-specific manner.
Båvner
Ann
A
Department of Biosciences at Novum, Karolinska Institutet S-14157 Huddinge, Sweden. ann.bavner@biosci.ki.se
Matthews
Jason
J
Sanyal
Sabyasachi
S
Gustafsson
Jan-Ake
JA
Treuter
Eckardt
E
D017500:Adenovirus E1A Proteins / Q000378:metabolism; D000818:Animals; D050882:CREB-Binding Protein; D002352:Carrier Proteins / Q000145:classification / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D003001:Cloning, Molecular; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D011401:Promoter Regions, Genetic; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D012097:Repressor Proteins; D013737:Testis / Q000378:metabolism; D015534:Trans-Activators / Q000037:antagonists & inhibitors* / Q000737:chemistry; D015533:Transcriptional Activation; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins
D017500:Adenovirus E1A Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C416925:EID1 protein, human; C502085:EID3 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; C051838:TFF1 protein, human; D015534:Trans-Activators; D000071163:Trefoil Factor-1; D025521:Tumor Suppressor Proteins; D050882:CREB-Binding Protein; C494363:CREBBP protein, human