Genome-wide crosstalk between progesterone receptor and estrogen receptor in preterm labor

Project: Research project

Description

Preterm birth (PTB, birth at <37 weeks of pregnancy) is the leading cause of newborn death and plays an important role in PTB associated complications including cerebral palsy, cognitive impairment, blindness, and deafness, et al. Drugs given to delay labor haven’t significantly reduced the PTB incidence. Our goal is to discover new targets for PTB therapy. Progesterone (P4) and estrogen (E2), through their receptors PR and ER, play dominant roles in pregnancy maintenance and labor initiation. PR and ER function by binding DNA regulatory regions of target genes and regulate their transcription. Studies demonstrate that PR and ER compete for binding to the same regulatory regions of certain genes responsible for transition from pregnant to laboring myometrium. Studies have also shown that histone (DNA compacting protein) modifications play important roles in regulating hormone receptor-mediated gene transcription. We hypothesize that the regulatory nodes composed of PR and ER interaction with DNA in combination with specific histone modification act as a powerful switch turning on/off genes critical for myometrium function. We will test our hypothesis by identifying global gene regulatory regions bound by hormone receptors and the specific histone modification in myometrial tissues derived from term not in labor and in labor as well as preterm in labor women. Meanwhile, we will define the gene transcription activities in these tissues. We anticipate that deciphering these regulatory nodes will move the field of PTB research far beyond the current limits of knowledge and identify new therapeutic targets to prevent it.
StatusActive
Effective start/end date1/1/174/30/20

Funding

  • University of Chicago (FP059028-E//22-FY18-809)
  • March of Dimes Foundation (FP059028-E//22-FY18-809)

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Premature Obstetric Labor
Progesterone Receptors
Estrogen Receptors
Genome
Nucleic Acid Regulatory Sequences
Histone Code
Genes
Myometrium
DNA
Deaf-Blind Disorders
Pregnancy Maintenance
Hormones
Premature Birth
Cerebral Palsy
Histones
Progesterone
Cause of Death
Estrogens
Parturition
Newborn Infant