The chromatin unfolding domain of chromosomal protein HMG-14 targets the N-terminal tail of histone H3 in nucleosomes

Abstract

Nonhistone chromosomal protein HMG-14 is a nucleosomal binding protein that unfolds the higher-order chromatin structure and enhances the transcriptional potential of chromatin, but not that of DNA. Both the transcriptional enhancement and the chromatin unfolding activities of HMG-14 are mediated through the C-terminal region of the protein. Here we study the molecular interactions of both this region and the N-terminal region of HMG-14 with nucleosome cores. By protein photocrosslinking we demonstrate that the N-terminal domain of HMG-14 targets a restricted region in histone H2B, whereas the C-terminal chromatin unfolding domain of HMG-14 targets a restricted region in the N terminus of histone H3. The N-terminal regions of the core histones are involved in the folding of oligonucleosomes and are the target of various activities associated with chromatin unfolding and transcriptional activation. We suggest that specific interactions between the C-terminal domain of HMG-14 and the N-terminal tail of histone H3 reduce the compaction of chromatin. These findings provide insights into the molecular mechanism whereby HMG-14͞-17 proteins reduce the repressive effect of chromatin, and they also broaden the scope of the molecular interactions involving the N termini of the core histones in nucleosomes.

Osmotic Stress-dependent Repression Is Mediated by Histone H3 Phosphorylation and Chromatin Structure

“…The HMGN1 protein is a component of normal chromatin structure that binds to nucleosome core particles and modifies chromatin compaction (17)(18)(19). The HMGN1-dependent changes in chromatin compaction regulate the access of kinases to histone H3.…”

“…In particular, HMGN1 binds specifically to nucleosomes and interacts with histones H1 and H3 (17,18). HMGN1 is phosphorylated in response to stress stimuli modifying both HMGN1 binding to the nucleosome and chromatin packing, which affects the ability of kinases to phosphorylate histone H3 (19,20).…”

Mammalian Transcription-Coupled Excision Repair

“…These involve the essential function of the Swi2/Snf2-like CSB protein, which has also been shown to have chromatin remodeling activity , the CSB-dependent recruitment of chromatin regulators such as the histone acetyltransferase (HAT) p300 (Fousteri et al 2006), and the enhancement of TC-NER on treatment of cells with histone deacetylase inhibitors (Smerdon et al 1982). Equally important is the recruitment of the nucleosomal nonhistone binding protein HMGN1 in a CSB-and CSA-dependent manner (Fousteri et al 2006), which is known to increase HAT activity and unwind chromatin (Trieschmann et al 1998;Lim et al 2005).…”

Chromosomal Protein HMGN1 Modulates the Phosphorylation of Serine 1 in Histone H2A

“…A central, positively charged region contains the major HMGN-chromatin contacts (16,17); however, additional sites of interactions have been identified. Thus, site-directed cross-linking of HMGN-nucleosome complexes indicates that the C-terminal region of HMGN1 is located near the amino terminal tail of histone H3 (17). Significantly, HMGN1 enhances the levels of acetylation in H3K14, reduces the level of phosphorylation of H3S10 and H3S28, and also changes the acetylation and methylation state of H3K9 (10).…”

“…HMGN proteins have a modular structure and contact both the nucleosomal DNA and the histone through multiple interaction sites (15). A central, positively charged region contains the major HMGN-chromatin contacts (16,17); however, additional sites of interactions have been identified. Thus, site-directed cross-linking of HMGN-nucleosome complexes indicates that the C-terminal region of HMGN1 is located near the amino terminal tail of histone H3 (17).…”