BACKGROUND: CTCF is a highly conserved and essential zinc finger protein 
expressed in virtually all cell types. In conjunction with cohesin, it organizes 
chromatin into loops, thereby regulating gene expression and epigenetic events. 
The function of CTCFL or BORIS, the testis-specific paralog of CTCF, is less 
clear.
RESULTS: Using immunohistochemistry on testis sections and fluorescence-based 
microscopy on intact live seminiferous tubules, we show that CTCFL is only 
transiently present during spermatogenesis, prior to the onset of meiosis, when 
the protein co-localizes in nuclei with ubiquitously expressed CTCF. CTCFL 
distribution overlaps completely with that of Stra8, a retinoic acid-inducible 
protein essential for the propagation of meiosis. We find that absence of CTCFL 
in mice causes sub-fertility because of a partially penetrant testicular 
atrophy. CTCFL deficiency affects the expression of a number of testis-specific 
genes, including Gal3st1 and Prss50. Combined, these data indicate that CTCFL 
has a unique role in spermatogenesis. Genome-wide RNA expression studies in ES 
cells expressing a V5- and GFP-tagged form of CTCFL show that genes that are 
downregulated in CTCFL-deficient testis are upregulated in ES cells. These data 
indicate that CTCFL is a male germ cell gene regulator. Furthermore, genome-wide 
DNA-binding analysis shows that CTCFL binds a consensus sequence that is very 
similar to that of CTCF. However, only ~3,700 out of the ~5,700 CTCFL- and 
~31,000 CTCF-binding sites overlap. CTCFL binds promoters with loosely assembled 
nucleosomes, whereas CTCF favors consensus sites surrounded by phased 
nucleosomes. Finally, an ES cell-based rescue assay shows that CTCFL is 
functionally different from CTCF.
CONCLUSIONS: Our data suggest that nucleosome composition specifies the 
genome-wide binding of CTCFL and CTCF. We propose that the transient expression 
of CTCFL in spermatogonia and preleptotene spermatocytes serves to occupy a 
subset of promoters and maintain the expression of male germ cell genes.