Microarray analysis of the transcriptional network controlled by the photoreceptor homeobox gene Crx.
BACKGROUND
Terminal differentiation of many cell types is controlled and maintained by tissue- or cell-specific transcription factors. Little is known, however, of the transcriptional networks controlled by such factors and how they regulate differentiation. The paired-type homeobox transcription factor, Crx, has a pivotal role in the terminal differentiation of vertebrate photoreceptors. Mutations in the human CRX gene result in either congenital blindness or photoreceptor degeneration and targeted mutation of the mouse Crx results in failure of development of the light-detecting outer segment of photoreceptors.


RESULTS
We have characterized the transcriptional network controlled by Crx by microarray analysis of gene expression in developing retinal tissue from Crx(+/+) and Crx(-/-) mice. These data were combined with analyses of gene expression in developing and adult retina, as well as adult brain. The most abundant elements of this network are ten photoreceptor-specific or -enriched genes, including six phototransduction genes. All of the available 5' regulatory regions of the putative Crx targets contain a novel motif that is composed of a head-to-tail arrangement of two Crx-binding-element-like sequences. Analysis of the 5' regions of a set of mouse and human genes suggests that this motif is specific to Crx targets.


CONCLUSIONS
This study demonstrates that cDNA microarrays can be successfully used to define the transcriptional networks controlled by transcription factors in vertebrate tissue in vivo.
Livesey
F J
FJ
Department of Genetics, Howard Hughes Medical Institute, Harvard Medical School, Boston 02115, USA.
Furukawa
T
T
Steffen
M A
MA
Church
G M
GM
Cepko
C L
CL
D000818:Animals; D002417:Cattle; D005786:Gene Expression Regulation; D005801:Genes, Homeobox; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020419:Photoreceptor Cells, Vertebrate; D012160:Retina; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic
D018398:Homeodomain Proteins; D015534:Trans-Activators; C109288:cone rod homeobox protein