Objective        To determine the effects of histone acetylation and H3 lysine 4 (H3K4) methylation on the ratio of A and B isoforms of the human progesterone receptor (PRA/PRB) in human uterine smooth muscle cells during the course of pregnancy.        Methods        Human uterine smooth muscle cells of pregnancy were isolated from 16 full-term pregnant women recei

ving caesarean section

and then purified by collagenase digestion. The expression of PR and PRB was detected by immunohistochemistry in the cells and in the cells treated with different concentrations of histone deacetylase inhibitor

trichostatin A (TSA) or H3K4 methyltransferase inhibitor

5′-methylthioadenosine (MTA). The mRNA levels of PR

PRA and PRB were detected by real-time PCR. Chromatin immunoprecipitation (ChIP) was used to analyze acetylation of histones H3 and H4

and trimethylation of H3K4 in the promoter regions of PRA and PRB.        Results        TSA treatment resulted in obviously increase in the ratio of PRA/PRB (

P

0.05) and in the acetylation of histones H3 and H4 in the promoter region of PRA (

P

0.05). While

MTA treatment led the ratio of PRA/PRB significantly decreased (

P

0.05) and reduced the trimethylation of H3K4 in the promoter region of PRA (

P

0.05). Both TSA and MTA regulated the expression of PRA to exert effect on the ratio of PRA/PRB.        Conclusion       Both the acetylation of histones H3 and H4 and the methylation of H3K4 regulate the ratio of PRA/PRB

and might be involved in the mechanism of “functional progesterone withdrawal” in the human uterine smooth muscle cells of pregnancy.