Acetylation and deacetylation regulate CCAAT/enhancer binding protein beta at K39 in mediating gene transcription.
The transcription factor CCAAT/enhancer binding protein beta (C/EBPbeta) contains multiple acetylation sites, including lysine (K) 39. Mutation of C/EBPbeta at K39, an acetylation site in the transcriptional activation domain, impairs transcription of C/EBPbeta target genes in a dominant-negative fashion. Further, K39 of C/EBPbeta can be deacetylated by HDAC1, and HDAC1 may decrease C/EBPbeta-mediated transcription, suggesting that acetylation of C/EBPbeta at K39 is dynamically regulated in mediating gene transcription. Acetylation of endogenous C/EBPbeta at K39 is detected in adipose tissue, and also occurs in 3T3-L1 cells undergoing adipocyte conversion. In addition, mutation of K39 in C/EBPbeta impairs activation of its target genes encoding C/EBPalpha and PPARgamma, essential mediators of adipogenesis, as well as adipocyte genes for leptin and Glut4. These findings suggest that acetylation of C/EBPbeta at K39 is an important and dynamic regulatory event that contributes to its ability to transactivate target genes, including those associated with adipogenesis and adipocyte function.
Ceseña
Teresa I
TI
Cellular & Molecular Biology Program, University of Michigan, Ann Arbor, MI 48109-5622, United States.
Cui
Tracy X
TX
Subramanian
Lalitha
L
Fulton
Christina T
CT
Iñiguez-Lluhí
Jorge A
JA
Kwok
Roland P S
RP
Schwartz
Jessica
J
D041721:3T3-L1 Cells; D000107:Acetylation; D000273:Adipose Tissue / Q000502:physiology; D000818:Animals; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000737:chemistry* / Q000235:genetics*; D016466:CHO Cells; D002454:Cell Differentiation; D006224:Cricetinae; D003412:Cricetulus; D051379:Mice; D009154:Mutation; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D022763:CCAAT-Enhancer-Binding Protein-alpha; D022782:CCAAT-Enhancer-Binding Protein-beta; D047495:PPAR gamma