huASH1 protein, a putative transcription factor encoded by a human homologue of the Drosophila ash1 gene, localizes to both nuclei and cell-cell tight junctions
T. Nakamura et al., huASH1 protein, a putative transcription factor encoded by a human homologue of the Drosophila ash1 gene, localizes to both nuclei and cell-cell tight junctions, P NAS US, 97(13), 2000, pp. 7284-7289
Citations number
46
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
During animal development, regions of the embryo become committed to positi
on-specific: identities, which are determined by spatially restricted expre
ssion of Hox/homeotic genes. This expression pattern is initially establish
ed by the activity of the segmentation genes and is subsequently maintained
during the proliferative stage through the action of transcription factors
encoded by the trithorax (trx) and Polycomb (Pc) groups of genes. trithora
x (trx) and ash1 (absent, small, or homeotic 1) are members of the Drosophi
la trx group. Their products are associated with chromosomes and are believ
ed to activate transcription of target genes through chromatin remodeling.
Recently, we reported molecular studies indicating that TRX and ASH1 protei
ns act in concert to bind simultaneously to response elements located at cl
ose proximity within the same set of target genes. Extension of these and o
ther studies to mammalian systems required identification and cloning of th
e mammalian homologue of ash1 (the mammalian homologue of trx, ALL-1, was p
reviously cloned). We have identified a human expressed sequence tag (EST)
clone with similarity to the SET domain of Drosophila ASH1, and used it to
clone the human gene. huASH1 resides at chromosomal band 1q21. The gene is
expressed in multiple tissues as an approximate to 10.5-kb transcript and e
ncodes a protein of 2962 residues. The protein contains a SET domain, a PHD
finger, four AT hooks, and a region with homology to the bromodomain. The
last region is not present in Drosophila ASH1, and as such might confer to
the human protein a unique additional function, Using several anti-huASH1 A
b for immunostaining of cultured cells, we found that the protein is distri
buted in intranuclear speckles, and unexpectedly also in intercellular junc
tions. Double-immunofluorescence labeling of huASH1 and several junctional
proteins localized the huASH1 protein into tight junctions. The significanc
e of huASH1 dual location is discussed. In particular, we consider the poss
ibility that translocation of the protein between the junctional membrane a
nd the nucleus may be involved in adhesion-mediated signaling.