Role of Histone H1 as an Architectural Determinant of Chromatin Structure and as a Specific Repressor of Transcription onXenopus Oocyte 5S rRNA Genes

Abstract

We explore the role of histone H1 as a DNA sequence-dependent architectural determinant of chromatin structure and of transcriptional activity in chromatin. The Xenopus laevis oocyte-and somatic-type 5S rRNA genes are differentially transcribed in embryonic chromosomes in vivo depending on the incorporation of somatic histone H1 into chromatin. We establish that this effect can be reconstructed at the level of a single nucleosome. H1 selectively represses oocyte-type 5S rRNA genes by directing the stable positioning of a nucleosome such that transcription factors cannot bind to the gene. This effect does not occur on the somatic-type genes. Histone H1 binds to the 5 end of the nucleosome core on the somatic 5S rRNA gene, leaving key regulatory elements in the promoter accessible, while histone H1 binds to the 3 end of the nucleosome core on the oocyte 5S rRNA genes, specifically blocking access to a key promoter element (the C box). TFIIIA can bind to the somatic 5S rRNA gene assembled into a nucleosome in the presence of H1. Because H1 binds with equivalent affinities to nucleosomes containing either gene, we establish that it is the sequence-selective assembly of a specific repressive chromatin structure on the oocyte 5S rRNA genes that accounts for differential transcriptional repression. Thus, general components of chromatin can determine the assembly of specific regulatory nucleoprotein complexes.Determination of the structure of eukaryotic transcription factors has led to the recognition that several DNA recognition motifs are shared with proteins that are conventionally viewed as having the general function of packaging the vast majority of DNA within the chromosome (61,71,105). These similarities occur between the core histones and particular TATA binding protein-associated factors within transcription factor TFIID (3, 9, 118), between linker histones and sequence-specific DNA binding proteins such as hepatocyte nuclear factor 3 (HNF3) (15,72), and between high-mobility-group HMG1 and DNA binding proteins such as the human sex-determining factor SRY (73,103,105). The proteins that package DNA into the chromosome do so by bending or wrapping the double helix. Transcription factors that share structural features with histones or HMG proteins might function as architectural determinants that remodel DNA to facilitate the assembly of higher-order nucleoprotein structures that activate or repress transcription (4,24,26,30,31,51,109). HNF3, which contains a winged-helix motif similar to that found in histone H1, can replace H1 in the chromatin of the mouse serum albumin enhancer (53, 54). HNF3 contributes to the positioning of nucleosomes on this regulatory DNA (14, 81, 111).The core histones, linker histones, and HMG proteins could also contribute to the assembly of specific regulatory nucleoprotein architectures through structure-and sequence-selective interactions with DNA (87, 109, 112). Core histones may selectively recognize both DNA structure such as curvature (83, 112) and sequence (25, 101). Sequence-...

Histone H2A Ubiquitination Does Not Preclude Histone H1 Binding, but It Facilitates Its Association with the Nucleosome

“…Under the experimental conditions used by us, no evidence could be found for asymmetric protection of linker DNA as has been observed with Xenopus 5 S rDNA (25,62,63). Interestingly this chromatosome position in Xenopus 5 S rRNA has been found more recently to be susceptible to sequence-specific artifacts, and another major chromatosome position that involves protection of 20 bp on one side of the nucleosome has also been reported (24,64,65). If this type of protection were the case here, it implies that the incorporation of histone H1 led to a shift in the equilibrium position of nucleosomes from position A to position B. Alternatively, since nucleosomes are more mobile in the absence of linker histones (66), it is possible that digestion with micrococcal nuclease could induce short range sliding of nucleosomes.…”

Specific Binding of High-Mobility-Group I (HMGI) Protein and Histone H1 to the Upstream AT-Rich Region of the Murine Beta Interferon Promoter: HMGI Protein Acts as a Potential Antirepressor of the Promoter

“…Also, it has been shown that the histone H1-mediated repression of oocyte-type 5S rRNA genes is dependent upon the binding of histone H1 to the AT-rich flanking sequences of these genes (19,39). More recent work suggests that the specific transcriptional repressor effect of histone H1 on the Xenopus oocyte 5S rRNA gene is linked to the presence of an AT-rich sequence 3Ј to the gene as well as to the binding of histone H1 to the 3Ј end of the nucleosome core, blocking the access to a key promoter element (33). For Xenopus embryos, Vermaak et al have described the globular domain of histone H1 as being sufficient to direct this specific gene repression (40).…”

“…Distamycin has been described as a drug that can specifically displace histone H1 from oligo(dA) ⅐ oligo(dT) runs (17,33). In the case of the wild-type muIFN-␤ promoter integrated into chromatin, distamycin was able to activate the promoter after virus infection but only if the promoter carried the upstream AT-rich region (Fig.…”

Human SWI/SNF Drives Sequence-Directed Repositioning of Nucleosomes on C-myc Promoter DNA Minicircles

“…(24,25,45,(47)(48)(49)(50)), suggesting that mammalian body temperature might promote some level of nucleosome redistribution in vivo. Thermal repositioning is most rapid at high temperatures (up to 65°C) and in the absence of divalent cations or linker histones (45,48,51,52)). In general, thermal repositioning appears to result in redistribution between sites that are all at least moderately-favored during nucleosome assembly (causing increases in some moderately favored positions and decreases in some strongly favored positions).…”