Characterization of ESE-2, a novel ESE-1-related Ets transcription factor that is restricted to glandular epithelium and differentiated keratinocytes.
Epithelial cell differentiation is tightly controlled by distinct sets of transcription factors that regulate the expression of stage-specific genes. We recently isolated the first epithelium-specific Ets transcription factor (ESE-1). Here we describe the characterization of ESE-2, a second epithelium-restricted ESE-1-related Ets factor. Like ESE-1, ESE-2 is induced during keratinocyte differentiation. However, whereas ESE-1 is expressed in the majority of epithelial cell types, ESE-2 expression is restricted to differentiated keratinocytes and glandular epithelium such as salivary gland, prostate, mammary gland, and kidney. In contrast to ESE-1, full-length ESE-2 binds poorly to DNA due to the presence of a negative regulatory domain at the amino terminus. Furthermore, although ESE-1 and the amino-terminally deleted ESE-2 bind with similar affinity to the canonical E74 Ets site, ESE-2 and ESE-1 differ strikingly in their relative affinity toward binding sites in the c-MET and PSMA promoters. Similarly, ESE-1 and ESE-2 drastically differ in their ability to transactivate epithelium-specific promoters. Thus, ESE-2, but not ESE-1, transactivates the parotid gland-specific PSP promoter and the prostate-specific PSA promoter. In contrast, ESE-1 transactivates the keratinocyte-specific SPRR2A promoter Ets site and the prostate-specific PSMA promoter significantly better than ESE-2. Our results demonstrate the existence of a unique class of related epithelium-specific Ets factors with distinct functions in epithelial cell gene regulation.
Oettgen
P
P
New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
Kas
K
K
Dube
A
A
Gu
X
X
Grall
F
F
Thamrongsak
U
U
Akbarali
Y
Y
Finger
E
E
Boltax
J
J
Endress
G
G
Munger
K
K
Kunsch
C
C
Libermann
T A
TA
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D055233:Cornified Envelope Proline-Rich Proteins; D004268:DNA-Binding Proteins; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D015603:Keratinocytes; D008565:Membrane Proteins / Q000235:genetics; D008969:Molecular Sequence Data; D010306:Parotid Gland; D011401:Promoter Regions, Genetic; D017430:Prostate-Specific Antigen / Q000235:genetics; D011498:Protein Precursors / Q000235:genetics; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid; D012471:Salivary Proteins and Peptides / Q000235:genetics; D016415:Sequence Alignment; D015534:Trans-Activators / Q000737:chemistry; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics*; D015533:Transcriptional Activation / Q000235:genetics*
C045623:BPIFA2 protein, human; D055233:Cornified Envelope Proline-Rich Proteins; D004268:DNA-Binding Proteins; C105529:ELF3 protein, human; C116038:ELF5 protein, human; D008565:Membrane Proteins; D011498:Protein Precursors; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; C101744:SPRR2A protein, human; D012471:Salivary Proteins and Peptides; D015534:Trans-Activators; D014157:Transcription Factors; D017430:Prostate-Specific Antigen