Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4.
The transcription factors HNF3 (FoxA) and GATA-4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in embryos. To understand how they access sites in silent chromatin, we assembled nucleosome arrays containing albumin enhancer sequences and compacted them with linker histone. HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes. The ability of HNF3 to open chromatin is mediated by a high affinity DNA binding site and by the C-terminal domain of the protein, which binds histones H3 and H4. Thus, factors that potentiate transcription in development are inherently capable of initiating chromatin opening events.
Cirillo
Lisa Ann
LA
Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA.
Lin
Frank Robert
FR
Cuesta
Isabel
I
Friedman
Dara
D
Jarnik
Michal
M
Zaret
Kenneth S
KS
D020816:Amino Acid Motifs; D000818:Animals; D001665:Binding Sites; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism; D002843:Chromatin / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000502:physiology*; D004707:Endoderm / Q000378:metabolism; D004742:Enhancer Elements, Genetic / Q000502:physiology; D005326:Fetal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D050991:GATA4 Transcription Factor; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020868:Gene Silencing; D051541:Hepatocyte Nuclear Factor 3-alpha; D006657:Histones / Q000502:physiology*; D008099:Liver / Q000196:embryology / Q000378:metabolism; D046911:Macromolecular Substances; D051379:Mice; D008957:Models, Genetic; D025542:Neurofibromin 1 / Q000378:metabolism; D009687:Nuclear Proteins / Q000737:chemistry / Q000502:physiology*; D009707:Nucleosomes / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012709:Serum Albumin / Q000096:biosynthesis / Q000235:genetics; D013329:Structure-Activity Relationship; D014157:Transcription Factors / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D022782:CCAAT-Enhancer-Binding Protein-beta; D002843:Chromatin; D004268:DNA-Binding Proteins; D005326:Fetal Proteins; C496500:Foxa1 protein, mouse; D050991:GATA4 Transcription Factor; D051541:Hepatocyte Nuclear Factor 3-alpha; D006657:Histones; D046911:Macromolecular Substances; D025542:Neurofibromin 1; D009687:Nuclear Proteins; D009707:Nucleosomes; D011993:Recombinant Fusion Proteins; D012709:Serum Albumin; D014157:Transcription Factors