title: Characterization of ESE-2, a novel ESE-1-related Ets transcription factor that is restricted to glandular epithelium and differentiated keratinocytes.
abstract: 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.
authors.affiliation: New England Baptist Bone and Joint Institute, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: P
authors.initials: P
authors.lastname: Oettgen
authors.forename: K
authors.initials: K
authors.lastname: Kas
authors.forename: A
authors.initials: A
authors.lastname: Dube
authors.forename: X
authors.initials: X
authors.lastname: Gu
authors.forename: F
authors.initials: F
authors.lastname: Grall
authors.forename: U
authors.initials: U
authors.lastname: Thamrongsak
authors.forename: Y
authors.initials: Y
authors.lastname: Akbarali
authors.forename: E
authors.initials: E
authors.lastname: Finger
authors.forename: J
authors.initials: J
authors.lastname: Boltax
authors.forename: G
authors.initials: G
authors.lastname: Endress
authors.forename: K
authors.initials: K
authors.lastname: Munger
authors.forename: C
authors.initials: C
authors.lastname: Kunsch
authors.forename: T A
authors.initials: TA
authors.lastname: Libermann
mesh_terms: 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*
chemical_list: 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