title: Bioinformatic detection of E47, E2F1 and SREBP1 transcription factors as potential regulators of genes associated to acquisition of endometrial receptivity.
abstract: BACKGROUND
  The endometrium is a dynamic tissue whose changes are driven by the ovarian steroidal hormones. Its main function is to provide an adequate substrate for embryo implantation. Using microarray technology, several reports have provided the gene expression patterns of human endometrial tissue during the window of implantation. However it is required that biological connections be made across these genomic datasets to take full advantage of them. The objective of this work was to perform a research synthesis of available gene expression profiles related to acquisition of endometrial receptivity for embryo implantation, in order to gain insights into its molecular basis and regulation.
  
  
  METHODS
  Gene expression datasets were intersected to determine a consensus endometrial receptivity transcript list (CERTL). For this cluster of genes we determined their functional annotations using available web-based databases. In addition, promoter sequences were analyzed to identify putative transcription factor binding sites using bioinformatics tools and determined over-represented features.
  
  
  RESULTS
  We found 40 up- and 21 down-regulated transcripts in the CERTL. Those more consistently increased were C4BPA, SPP1, APOD, CD55, CFD, CLDN4, DKK1, ID4, IL15 and MAP3K5 whereas the more consistently decreased were OLFM1, CCNB1, CRABP2, EDN3, FGFR1, MSX1 and MSX2. Functional annotation of CERTL showed it was enriched with transcripts related to the immune response, complement activation and cell cycle regulation. Promoter sequence analysis of genes revealed that DNA binding sites for E47, E2F1 and SREBP1 transcription factors were the most consistently over-represented and in both up- and down-regulated genes during the window of implantation.
  
  
  CONCLUSIONS
  Our research synthesis allowed organizing and mining high throughput data to explore endometrial receptivity and focus future research efforts on specific genes and pathways. The discovery of possible new transcription factors orchestrating the CERTL opens new alternatives for understanding gene expression regulation in uterine function.
authors.affiliation: Instituto de Investigaciones Materno Infantil, Facultad de Medicina, Universidad de Chile, Santiago, Chile. atapiap@gmail.com
authors.forename: Alejandro
authors.initials: A
authors.lastname: Tapia
authors.forename: Cristian
authors.initials: C
authors.lastname: Vilos
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Marín
authors.forename: Horacio B
authors.initials: HB
authors.lastname: Croxatto
authors.forename: Luigi
authors.initials: L
authors.lastname: Devoto
mesh_terms: D019295:Computational Biology; D015536:Down-Regulation; D050687:E2F1 Transcription Factor / Q000235:genetics*; D010064:Embryo Implantation / Q000502:physiology*; D004717:Endometrium / Q000502:physiology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics*; D058127:Transcription Factor 3 / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; C497387:SREBF1 protein, human; D051780:Sterol Regulatory Element Binding Protein 1; D058127:Transcription Factor 3; D014157:Transcription Factors