Cooperation between C/EBPalpha TBP/TFIIB and SWI/SNF recruiting domains is required for adipocyte differentiation.

Chromatin remodeling is an important step in promoter activation during cellular lineage commitment and differentiation. We show that the ability of the C/EBPalpha transcription factor to direct adipocyte differentiation of uncommitted fibroblast precursors and to activate SWI/SNF-dependent myeloid-specific genes depends on a domain, C/EBPalpha transactivation element III (TE-III), that binds the SWI/SNF chromatin remodeling complex. TE-III collaborates with C/EBPalpha TBP/TFIIB interaction motifs during induction of adipogenesis and adipocyte-specific gene expression. These results indicate that C/EBPalpha acts as a lineage-instructive transcription factor through SWI/SNF-dependent modification of the chromatin structure of lineage-specific genes, followed by direct promoter activation via recruitment of the basal transcription-initiation complex, and provide a mechanism by which C/EBPalpha can mediate differentiation along multiple cellular lineages.

[1]  J. Mandel,et al.  The glyceraldehyde 3 phosphate dehydrogenase gene family: structure of a human cDNA and of an X chromosome linked pseudogene; amazing complexity of the gene family in mouse. , 1984, The EMBO journal.

[2]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[3]  M. Ringwald,et al.  Synergistic activation of the chicken mim‐1 gene by v‐myb and C/EBP transcription factors. , 1993, The EMBO journal.

[4]  T. Graf,et al.  Chicken hematopoietic cells transformed by seven strains of defective avian leukemia viruses display three distinct phenotypes of differentiation , 1979, Cell.

[5]  S. Freytag,et al.  Ectopic expression of the CCAAT/enhancer-binding protein alpha promotes the adipogenic program in a variety of mouse fibroblastic cells. , 1994, Genes & development.

[6]  B. Spiegelman,et al.  Cross-Regulation of C/EBPα and PPARγ Controls the Transcriptional Pathway of Adipogenesis and Insulin Sensitivity , 1999 .

[7]  O. MacDougald,et al.  Glycogen Synthase Kinase 3 Is an Insulin-Regulated C/EBPα Kinase , 1999, Molecular and Cellular Biology.

[8]  T. Graf,et al.  Identification of genes differentially expressed in two types of v-myb-transformed avian myelomonocytic cells. , 1992, Oncogene.

[9]  H. Land,et al.  Advanced mammalian gene transfer: high titre retroviral vectors with multiple drug selection markers and a complementary helper-free packaging cell line. , 1990, Nucleic acids research.

[10]  E. Ziff,et al.  Three levels of functional interaction determine the activity of CCAAT/enhancer binding protein-alpha on the serum albumin promoter. , 1994, Genes & development.

[11]  Peter F. Johnson,et al.  C/EBPβ, When Expressed from the C/ebpα Gene Locus, Can Functionally Replace C/EBPα in Liver but Not in Adipose Tissue , 2000, Molecular and Cellular Biology.

[12]  K. Chien,et al.  PPARγ Is Required for Placental, Cardiac, and Adipose Tissue Development , 1999 .

[13]  A. Bradley,et al.  Impaired energy homeostasis in C/EBP alpha knockout mice , 1995, Science.

[14]  T. Kirchgessner,et al.  Human lipoprotein lipase complementary DNA sequence. , 1987, Science.

[15]  T. Graf,et al.  Myb and NF-M: combinatorial activators of myeloid genes in heterologous cell types. , 1993, Genes & development.

[16]  S. McKnight,et al.  Identification of two polypeptide segments of CCAAT/enhancer-binding protein required for transcriptional activation of the serum albumin gene. , 1990, Genes & development.

[17]  B. Spiegelman,et al.  PPARγ Is Required for the Differentiation of Adipose Tissue In Vivo and In Vitro , 1999 .

[18]  D. Tenen,et al.  Absence of granulocyte colony-stimulating factor signaling and neutrophil development in CCAAT enhancer binding protein alpha-deficient mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[19]  S. McKnight,et al.  Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins. , 1995, Genes & development.

[20]  Michael R. Green,et al.  Facilitated binding of TATA-binding protein to nucleosomal DNA , 1994, Nature.

[21]  T. Graf,et al.  DNA binding by c‐Ets‐1, but not v‐Ets, is repressed by an intramolecular mechanism. , 1992, The EMBO journal.

[22]  B. Emerson,et al.  A SWI/SNF–Related Chromatin Remodeling Complex, E-RC1, Is Required for Tissue-Specific Transcriptional Regulation by EKLF In Vitro , 1998, Cell.

[23]  E. Querfurth,et al.  Antagonism between C/EBPbeta and FOG in eosinophil lineage commitment of multipotent hematopoietic progenitors. , 2000, Genes & development.

[24]  Z. Wu,et al.  Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. , 1995, Genes & development.

[25]  T. Graf,et al.  Distinct C/EBP functions are required for eosinophil lineage commitment and maturation. , 1998, Genes & development.

[26]  A. Leutz,et al.  Chromatin remodeling in development and differentiation. , 2001, Current opinion in genetics & development.

[27]  B. Porse,et al.  E2F Repression by C/EBPα Is Required for Adipogenesis and Granulopoiesis In Vivo , 2001, Cell.

[28]  J. Ntambi,et al.  Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. , 1989, Genes & development.

[29]  S. Orkin,et al.  Lethal β-thalassaemia in mice lacking the erythroid CACCC-transcription factor EKLF , 1995, Nature.

[30]  B. Lowell An Essential Regulator of Adipogenesis and Modulator of Fat Cell Function: PPARγ , 1999, Cell.

[31]  M. Lane,et al.  Cell-free transcription directed by the 422 adipose P2 gene promoter: activation by the CCAAT/enhancer binding protein. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[32]  A. Leutz,et al.  Novel mechanism of C/EBP beta (NF-M) transcriptional control: activation through derepression. , 1994, Genes & development.

[33]  D. Tenen,et al.  CCAAT/Enhancer Binding Protein α Is a Regulatory Switch Sufficient for Induction of Granulocytic Development from Bipotential Myeloid Progenitors , 1998, Molecular and Cellular Biology.

[34]  E. Ziff,et al.  CCAAT/enhancer binding protein‐alpha amino acid motifs with dual TBP and TFIIB binding ability co‐operate to activate transcription in both yeast and mammalian cells. , 1995, The EMBO journal.

[35]  M. R. Murphy,et al.  Targeting a SWI/SNF-related chromatin remodeling complex to the beta-globin promoter in erythroid cells. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[36]  A. Imbalzano,et al.  Mammalian SWI/SNF complexes promote MyoD-mediated muscle differentiation , 2001, Nature Genetics.

[37]  B. Spiegelman,et al.  Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[38]  Achim Leutz,et al.  A C/EBPβ Isoform Recruits the SWI/SNF Complex to Activate Myeloid Genes , 1999 .