PMID- 11466227
OWN - NLM
STAT- MEDLINE
DCOM- 20010927
LR  - 20190513
IS  - 0006-3363 (Print)
IS  - 0006-3363 (Linking)
VI  - 65
IP  - 2
DP  - 2001 Aug
TI  - Role of the transcriptional coactivator CBP/p300 in linking basic 
      helix-loop-helix and CREB responses for follicle-stimulating hormone-mediated 
      activation of the transferrin promoter in Sertoli cells.
PG  - 568-74
AB  - Sertoli cells are the epithelial cells responsible for the onset of pubertal 
      development and the maintenance of spermatogenesis in the adult. Transferrin is 
      one of the major secretory products expressed by differentiated Sertoli cells. 
      Investigation of the transcriptional control of transferrin gene expression 
      provides insight regarding the regulation of Sertoli cell differentiation. The 
      optimal activation of the mouse transferrin promoter (mTf) by FSH requires the 
      synergistic actions of the cAMP response element-binding protein (CREB) binding 
      to the cAMP response element-like proximal region II (PRII) and the basic 
      helix-loop-helix (bHLH) binding to the E-box. Proximal region II alone is 
      sufficient for cAMP-mediated activation. The proximity of the PRII and E-box (220 
      base pairs apart) suggests the possibility of interaction between CREB and bHLH 
      proteins. Such an interaction can be mediated by transcriptional integrators such 
      as CREB-binding protein (CBP) and/or p300 and may stabilize the binding of 
      trans-acting factors to their respective cis-elements. Such an interaction may 
      also provide a mechanism for cell-specific promoter activation. The hypothesis 
      tested in this study was that CBP/p300 is required for the synergistic activation 
      of the transferrin promoter involving PRII and E-box through the formation of a 
      ternary complex. In the Sertoli cells, both CBP and p300 proteins are expressed. 
      The effect of CBP/p300 on transferrin promoter activation and, hence, Sertoli 
      cell function was studied by using antisense oligonucleotides (AS-oligo). In the 
      presence of CBP/p300 AS-oligo, activity of the FSH-induced mTf-chloramphenicol 
      acetyl transferase (CAT) was significantly lower as compared to the respective 
      controls. Interestingly, AS-oligo had no effect on cAMP-induced activation of the 
      transferrin promoter reporter construct (mTf-CAT). Mutations in the E-box (EB*) 
      significantly reduced the FSH response. The presence of AS-oligo had no further 
      effect on the FSH-mediated activation of the EB*-mTf-CAT construct but reduced 
      cAMP-mediated activation. Mutations in the CRE-like PRII (PRII*) also 
      significantly reduced the FSH response. Activation of the PRII*-mTf-CAT in 
      response to cAMP was completely abolished. The presence of AS-oligo had no 
      further effect on the FSH- or cAMP-mediated activation of the PRII*-mTf-CAT 
      construct. In Sertoli cells, CBP/p300 was coimmunoprecipitated with CREB and the 
      bHLH protein E47. These observations suggest that CBP/p300 appears to be involved 
      in regulating FSH-mediated activation of the transferrin promoter by linking bHLH 
      and CREB activities.
FAU - Chaudhary, J
AU  - Chaudhary J
AD  - Center for Reproductive Biology, School of Molecular Biosciences, Washington 
      State University, Pullman, Washington 99164-4231, USA.
FAU - Skinner, M K
AU  - Skinner MK
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Biol Reprod
JT  - Biology of reproduction
JID - 0207224
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (Transferrin)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - 9002-68-0 (Follicle Stimulating Hormone)
RN  - EC 2.3.1.48 (E1A-Associated p300 Protein)
RN  - EC 2.3.1.48 (Ep300 protein, rat)
SB  - IM
MH  - Animals
MH  - Bucladesine/pharmacology
MH  - Cyclic AMP Response Element-Binding Protein/*metabolism
MH  - E1A-Associated p300 Protein
MH  - Follicle Stimulating Hormone/*pharmacology
MH  - Helix-Loop-Helix Motifs
MH  - Immunosorbent Techniques
MH  - Male
MH  - Nuclear Proteins/analysis/*physiology
MH  - *Promoter Regions, Genetic
MH  - Rats
MH  - Response Elements
MH  - Sertoli Cells/chemistry/*metabolism
MH  - Trans-Activators/analysis/*physiology
MH  - Transfection
MH  - Transferrin/*genetics
EDAT- 2001/07/24 10:00
MHDA- 2001/09/28 10:01
CRDT- 2001/07/24 10:00
PHST- 2001/07/24 10:00 [pubmed]
PHST- 2001/09/28 10:01 [medline]
PHST- 2001/07/24 10:00 [entrez]
AID - 10.1095/biolreprod65.2.568 [doi]
PST - ppublish
SO  - Biol Reprod. 2001 Aug;65(2):568-74. doi: 10.1095/biolreprod65.2.568.