Expression and interaction of the transcriptional coregulators, CBP/p300, in the human myometrium during pregnancy and labor.
OBJECTIVE
In humans, the factors that govern the switch from myometrial quiescence to coordinated contractions at the initiation of labor are not well defined. Recent studies have highlighted a role for the coactivator, CREB binding protein (CBP), in the human myometrium during pregnancy and labor through its ability to acetylate histones. In the present study, the expression of CBP and its related coactivator, p300, were examined.


METHODS
Levels and interactions of CBP and its paralogue p300 were determined by Western blotting, immunohistochemistry, and coimmunoprecipitation experiments using myometrial biopsy samples from nonpregnant (NP), pregnant nonlaboring (P), and spontaneously laboring (SL) women.


RESULTS
Levels of CBP were seen to increase in term P myometrial samples but were then greatly reduced in SL myometrium. In contrast, levels of p300 remained uniform between NP, P, and SL tissues. These observations were confirmed by immunhistochemical analyses. Immunoprecipitation experiments highlighted that CBP was able to interact with CREB, CREM, ATF-2, and p300 in P lower segment myometrium.


CONCLUSIONS
Recent evidence suggests that competition for CBP plays an important role in regulating gene expression during cell growth. Consequently our data suggest that the increase in myometrial CBP levels during pregnancy may occur to meet this increase in CBP demand. Moreover, from coimmunoprecipitation experiments, this increase in CBP expression would be expected to facilitate the transactivation potential of the cyclic adenosine monophosphate (cAMP)-dependent transcription factors CREB, CREM, and ATF-2.
Long
Audrey A
AA
School of Surgical and Reproductive Sciences (Obstetrics and Gynaecology), University of Newcastle-upon-Tyne, Newcastle-upon-Tyne, United Kingdom.
Chapman
Neil R
NR
Innes
Barbara
B
Europe-Finner
G Nicholas
GN
Robson
Stephen C
SC
D000328:Adult; D015153:Blotting, Western; D050882:CREB-Binding Protein; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D007743:Labor, Obstetric / Q000378:metabolism* / Q000502:physiology; D008875:Middle Aged; D009215:Myometrium / Q000378:metabolism* / Q000502:physiology; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011247:Pregnancy; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D000071701:Regulatory Factor X Transcription Factors; D015534:Trans-Activators; D014157:Transcription Factors; D051786:Cyclic AMP Response Element Modulator; D050882:CREB-Binding Protein; C494363:CREBBP protein, human