[Recognition of the potential SF-1 binding sites by SiteGA method, their experimental verification and search for new SF-1 target genes].
The SF-1 (Steroidogenic Factor-1) is a transcription factor known as a key regulator of the steroidogenic gene expression. SF-1 is required for the development and functioning at all levels of the hypothalamic-pituitary-gonadal and adrenal axis. Also it plays an essential role in sex determination. SF-1 is a member of the nuclear receptor superfamily and it activates gene expression by binding to DNA in a monomeric form. Here, we report the results of potential SF-1 binding sites identification by using the SiteGA recognition method. The SiteGA method was implemented using a genetic algorithm (GA) involving a iterative discriminant analyses of local dinucleotide context characteristics. These characteristics were compiled not only over the core binding sites region but over its flanks as well. Developed SiteGA method is characterized by considerably better recognition accuracy when compared to that for the weight matrix method. The experimental tests demonstrated that 83% of the sites recognized by the SiteGA method in the regulatory regions of steroidogenic genes, indeed, interact with the SF-1 factor. We also estimated the density of predicted sites in regulatory region of genes, the members of different functional groups and developed the criterion to search for new SF-1 target genes in genome sequences.
Klimova
N V
NV
Levitskiĭ
V G
VG
Ignat'eva
E V
EV
Vasil'ev
G V
GV
Kobzev
V F
VF
Busygina
T V
TV
Merkulova
T I
TI
Kolchanov
N A
NA
D000465:Algorithms; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D015894:Genome, Human / Q000502:physiology*; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D011237:Predictive Value of Tests; D011485:Protein Binding / Q000502:physiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D020218:Response Elements / Q000502:physiology*; D017422:Sequence Analysis, DNA; D012756:Sheep; D054339:Steroidogenic Factor 1; D013552:Swine; D014157:Transcription Factors / Q000378:metabolism*
D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse