Role of the POZ zinc finger transcription factor FBI-1 in human and murine adipogenesis.
Poxvirus zinc finger (POZ) zinc finger domain transcription factors have been shown to play a role in the control of growth arrest and differentiation in several types of mesenchymal cells but not, as yet, adipocytes. We found that a POZ domain protein, factor that binds to inducer of short transcripts-1 (FBI-1), was induced during both murine and human preadipocyte differentiation with maximal expression levels seen at days 2-4. FBI-1 mRNA was expressed in human adipose tissue with the highest levels found in samples from morbidly obese subjects. Murine cell lines constitutively expressing FBI-1 showed evidence for accelerated adipogenesis with earlier induction of markers of differentiation and enhanced lipid accumulation, suggesting that FBI-1 may be an active participant in the differentiation process. Consistent with the properties of this family of proteins in other cell systems, 3T3L1 cells stably overexpressing FBI-1 showed reduced DNA synthesis and reduced expression of cyclin A, cyclin-dependent kinase 2, and p107, proteins known to be involved in the regulation of mitotic clonal expansion. In addition, FBI-1 reduced the transcriptional activity of the cyclin A promoter. Thus, FBI-1, a POZ zinc finger transcription factor, is induced during the early phases of human and murine preadipocyte differentiation where it may contribute to adipogenesis through influencing the switch from cellular proliferation to terminal differentiation.
Laudes
Matthias
M
Department of Clinical Biochemistry, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QR, United Kingdom.
Christodoulides
Constantinos
C
Sewter
Ciaran
C
Rochford
Justin J
JJ
Considine
Robert V
RV
Sethi
Jaswinder K
JK
Vidal-Puig
Antonio
A
O'Rahilly
Stephen
S
D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D051379:Mice; D008938:Mitosis; D020411:Oligonucleotide Array Sequence Analysis; D012097:Repressor Proteins / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000502:physiology*; D016335:Zinc Fingers
D017931:DNA Primers; D004268:DNA-Binding Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; C485514:ZBTB7A protein, human; C117093:Zbtb7a protein, mouse