The expression of a novel, epithelium-specific ets transcription factor is restricted to the most differentiated layers in the epidermis.
Ets proteins have been implicated in the regulation of gene expression during a variety of biological processes, including growth control, differentiation, development and transformation. More than 35 related proteins containing the 'ets domain' have now been found which specifically interact with DNA sequences encompassing the core tetranucleotide GGAA. Although ets responsive genes have been identified in the epidermis, little is known about their distribution and function in this tissue. We have now demonstrated that epidermis and cultured epidermal keratinocytes synthesize numerous ets proteins. The expression of some of these proteins is regulated as a function of differentiation. Among these is a novel ets transcription factor with a dual DNA-binding specificity, which we have called jen. The expression of jen is not only epithelial specific, but it is the only ets protein so far described, and one of the very few transcription factors whose expression is restricted to the most differentiated epidermal layers. We show that two epidermal marker genes whose expression coincides with that of jen are transregulated by this protein in a complex mode which involves interactions with other transcriptional regulators such as Sp1 and AP1.
Andreoli
J M
JM
Laboratory of Skin Biology, NIAMS, NIH, Bethesda, MD 20892-2752, USA.
Jang
S I
SI
Chung
E
E
Coticchia
C M
CM
Steinert
P M
PM
Markova
N G
NG
D000328:Adult; D000595:Amino Acid Sequence; D001483:Base Sequence; D002454:Cell Differentiation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins; D000078404:Epidermal Cells; D004817:Epidermis / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D000091344:Filaggrin Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007381:Intermediate Filament Proteins / Q000235:genetics; D015603:Keratinocytes / Q000737:chemistry; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000032:analysis; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D012867:Skin / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D014157:Transcription Factors / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D004247:DNA