Structural and functional features of a specific nucleosome containing a recognition element for the thyroid hormone receptor.
The Xenopus thyroid hormone receptor betaA (TRbetaA) gene contains an important thyroid hormone response element (TRE) that is assembled into a positioned nucleosome. We determine the translational position of the nucleosome containing the TRE and the rotational positioning of the double helix with respect to the histone surface. Histone H1 is incorporated into the nucleosome leading to an asymmetric protection to micrococcal nuclease cleavage of linker DNA relative to the nucleosome core. Histone H1 association is without significant consequence for the binding of the heterodimer of thyroid hormone receptor and 9-cis retinoic acid receptor (TR/RXR) to nucleosomal DNA in vitro, or for the regulation of TRbetaA gene transcription following microinjection into the oocyte nucleus. Small alterations of 3 and 6 bp in the translational positioning of the TRE in chromatin are also without effect on the transcriptional activity of the TRbetaA gene, whereas a small change in the rotational position of the TRE (3 bp) relative to the histone surface significantly reduces the binding of TR/RXR to the nucleosome and decreases transcriptional activation directed by TR/RXR. Our results indicate that the specific architecture of the nucleosome containing the TRE may have regulatory significance for expression of the TRbetaA gene.
Wong
J
J
Laboratory of Molecular Embryology, National Institute of Child Health and Human Development, NIH, Building 18T, Room 106, Bethesda, MD 20892-5431, USA.
Li
Q
Q
Levi
B Z
BZ
Shi
Y B
YB
Wolffe
A P
AP
D000818:Animals; D001665:Binding Sites; D018983:DNA Footprinting; D005786:Gene Expression Regulation; D006657:Histones / Q000494:pharmacology; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011487:Protein Conformation; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000235:genetics* / Q000378:metabolism*; D012045:Regulatory Sequences, Nucleic Acid; D047488:Retinoid X Receptors; D017384:Sequence Deletion; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014981:Xenopus
D006657:Histones; D009707:Nucleosomes; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors