Alleviation of Histone H1-Mediated Transcriptional Repression and Chromatin Compaction by the Acidic Activation Region in Chromosomal Protein HMG-14

Abstract

Histone H1 promotes the generation of a condensed, transcriptionally inactive, higher-order chromatin structure. Consequently, histone H1 activity must be antagonized in order to convert chromatin to a transcriptionally competent, more extended structure. Using simian virus 40 minichromosomes as a model system, we now demonstrate that the nonhistone chromosomal protein HMG-14, which is known to preferentially associate with active chromatin, completely alleviates histone H1-mediated inhibition of transcription by RNA polymerase II. HMG-14 also partially disrupts histone H1-dependent compaction of chromatin. Both the transcriptional enhancement and chromatin-unfolding activities of HMG-14 are mediated through its acidic, C-terminal region. Strikingly, transcriptional and structural activities of HMG-14 are maintained upon replacement of the C-terminal fragment by acidic regions from either GAL4 or HMG-2. These data support the model that the acidic C terminus of HMG-14 is involved in unfolding higher-order chromatin structure to facilitate transcriptional activation of mammalian genes.In mammalian cells, genomic DNA is highly condensed, being organized in the nucleoprotein complex constituting chromatin (65,70). The packaging of genomic DNA into chromatin can inhibit gene expression in multiple ways: restricting the access of transcription factors to their promoter elements, blocking assembly and initiation by the general transcriptional machinery, and inhibiting elongation by the RNA polymerase. As a corollary, activation of transcription requires remodeling of the chromatin structure of the gene in order to relieve the repressive effects of chromatin on transcription (34,38,45,71,72).The building block of chromatin is the nucleosome, consisting of DNA wrapped twice around a histone octamer comprising the core histones H2A, H2B, H3, and H4. A linker histone, generally histone H1, interacts with DNA at several sites simultaneously (3, 51, 55, 58): (i) with DNA at or close to the entry and exit points of the nucleosome, (ii) with nucleosomal DNA over the dyad axis, after one wrap around the octamer, and (iii) with linker DNA between adjacent nucleosomal core particles. Within the interphase nucleus of higher eukaryotic cells, the linear array of nucleosomes is folded into a higherorder structure, called the 30-nm chromatin fiber (65, 70). Histone H1 plays a key role in the formation of such a higherorder chromatin structure (4, 37, 52, 59, 60).Biochemical and genetic studies have identified two distinct systems capable of remodeling the nucleosome structure for transcriptional activation. The multisubunit SWI/SNF complex, which is conserved from yeasts to humans (49, 69), can perturb the structure of a nucleosome in an ATP-dependent manner (15,29,35). This promotes the binding in vitro of either specific or general transcription factors, such as GAL4 and TBP, to their sites on nucleosomal DNA. A distinct nucleosome-remodeling factor (NURF), originally purified from Drosophila embryo extracts (63), is also capable ...

Architecture of the high mobility group nucleosomal protein 2-nucleosome complex as revealed by methyl-based NMR

“…6). These results are in line with the observations that HMGNs decrease the compaction of chromatin induced by linker histone H1 in vitro (8) and compete with histone H1 for binding to chromatin in vivo (29). Moreover, our results provide the structural basis for the release of HMGNs from chromatin upon phosphorylation of Ser24 and Ser28 during mitosis (30).…”

“…High mobility group nucleosomal (HMGN) proteins are a family of such proteins that exist in vertebrate. HMGNs decompact chromatin condensed by the linker histone H1 (8), thereby enhancing transcription activity of the chromatin template. In addition, HMGNs affect DNA repair (9), chromatin remodeling (10), and the extent of histone modifications (11).…”

cAMP-response Element-binding Protein (CREB) Controls MSK1-mediated Phosphorylation of Histone H3 at the c-fos Promoter in Vitro

“…This intrinsic nucleosomal barrier appears to be modulated to some extent by HMGN1, an architectural chromatin protein that binds to nucleosomes and decompacts chromatin (29,60,61). Although Lim et al (44) reported that HMGN1 diminishes the MSK1-mediated phosphorylation of histone H3 within a nucleosome core particle, our assays show that HMGN1 enhances the MSK1-mediated histone H3 phosphorylation in an activator-dependent manner on a reconstituted nucleosome array, a more physiological context in which HMGN1 interacts with nucleosomes in vivo.…”

“…HMGN1 consists of multiple domains, including the nucleosomal binding domain and chromatin unfolding domain (60,61). Because the chromatin unfolding domain is located near, and probably interacts with, the residues 20 -50 of histone H3 (62), this domain may directly shift the position of the histone H3 tail in a manner that would facilitate H3-S10 phosphorylation by MSK1.…”

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

“…As a matter of fact, upstream binding factor 3, a high-mobility-grouplike protein, displaces and causes complete dissociation of histone H1 from rRNA gene enhancers associated with nucleosomes (18). Ding et al have demonstrated that histone H1 can be a functional target of high-mobility-group protein 14 in both transcriptional enhancement and chromatin decompaction (10). Hepatocyte nuclear factor 3 has a configuration very similar to that of histone H1 and, like histone H1, has nucleosome positioning properties (28).…”