Krtap16, characterization of a new hair keratin-associated protein (KAP) gene complex on mouse chromosome 16 and evidence for regulation by Hoxc13.
Intermediate filament (IF) keratins and keratin-associated proteins (KAPs) are principal structural components of hair and encoded by members of multiple gene families. The severe hair growth defects observed upon aberrant expression of certain keratin and KAP genes in both mouse and man suggest that proper hair growth requires their spatio-temporally coordinated activation. An essential prerequisite for studying these cis-regulatory mechanisms is to define corresponding gene families, their genomic organization, and expression patterns. This work characterizes eight recently identified high glycine/tyrosine (HGT)-type KAP genes collectively designated Krtap16-n. These genes are shown to be integrated into a larger KAP gene domain on mouse chromosome 16 (MMU16) that is orthologous to a recently described HGT- and high sulfur (HS)-type KAP gene complex on human chromosome 21q22.11. All Krtap16 genes exhibit strong expression in a narrowly defined pattern restricted to the lower and middle cortical region of the hair shaft in both developing and cycling hair. During hair follicle regression (catagen), expression levels decrease until expression is no longer detectable in follicles at resting stage (telogen). Since isolation of the Krtap16 genes was based on their differential expression in transgenic mice overexpressing the Hoxc13 transcriptional regulator in hair, we examined whether bona fide Hoxc13 binding sites associated with these genes might be functionally relevant by performing electrophoretic mobility shift assays (EMSAs). The data provide evidence for sequence-specific interaction between Hoxc13 and Krtap16 genes, thus supporting the concept of a regulatory relationship between Hoxc13 and these KAP genes.
Pruett
Nathanael D
ND
Department of Medicine, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Tkatchenko
Tatiana V
TV
Jave-Suarez
Luis
L
Jacobs
Donna F
DF
Potter
Christopher S
CS
Tkatchenko
Andrei V
AV
Schweizer
Jürgen
J
Awgulewitsch
Alexander
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000737:chemistry* / Q000235:genetics*; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D017124:Conserved Sequence; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D005786:Gene Expression Regulation; D006197:Hair / Q000378:metabolism*; D018398:Homeodomain Proteins / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D005810:Multigene Family; D009841:Oligonucleotides / Q000737:chemistry; D010802:Phylogeny; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013997:Time Factors
D002352:Carrier Proteins; D018076:DNA, Complementary; D018398:Homeodomain Proteins; C485834:Hoxc13 protein, mouse; D009841:Oligonucleotides; D007633:Keratins; D004247:DNA