Hyper(ADP-ribosyl)ation of histone H1

Abstract

Nucleosomal chains of various repeat unit lengths were generated by a mild micrococcal nuclease digestion of purified pancreatic nuclei. Maximal nucleosome associated poly(ADP-ribose) polymerase activity was recovered in trimeric to tetrameric chromatin fragments, after which the enzyme activity gradually decreased and stabilized towards oligomeric periodicities of 11 to 16 nucleosomes. Electrophoresis of [32P]ADP-ribosylated histones on first-dimension acid-urea or acid-urea-Triton gels and on second-dimension acid--urea--cetyltriammonium bromide gels revealed that, of all histones, only histone H1 could be significantly poly(ADP-ribosyl)ated while only minimal modification could be recovered with histone H1(0). Furthermore, the extent of ADP-ribosylation present on pancreatic histone H1 is shown to proportionally retard this protein's electrophoretic mobility in all gel systems and to consist of a distinct series of at least 12 modification intermediates which can be evidenced, in nuclei or nucleosomes, and fully recovered along with histone H1 upon its selective extraction with 5% perchloric acid. The generation of these increasingly ADP-ribosylated forms of histone H1 is also demonstrated to be time dependent and the more complex ADP-ribosylated forms of this histone are favored at high NAD+ concentrations. Moreover, the electrophoretic mobilities of all intermediates are unaffected by the presence of the nonionic detergent Triton X-100.

Poly(ADP-ribosyl)ation of polynucleosomes causes relaxation of chromatin structure.

“…Note that purified calf thymus poly(ADP-ribose) polymerase has preferentially poly(ADP-ribosyl)ated histone Hi, as previously observed with the endogenous pancreatic enzyme (11,25).…”

Signaling Mechanism of Poly(ADP-Ribose) Polymerase-1 (PARP-1) in Inflammatory Diseases

“…For function on chromatin-remodeling regulation, it is suggested that in the presence of saturating NAD ϩ , PARP-1-dependent attachment of PARs to core histones and the linker histone H1 15,72 introduces massive negative charges and facilitates relaxation of the chromatin superstructure and recruitment of transcription machinery to the promoter or enhancer of target genes. 73,74 The literature provides evidence that the effects of PARP-1 on transcription factors regulating inflammatory cytokine gene expression vary diversely, depending on the stimuli and cell and tissue types. For example, PARP-1 has been implicated in the activation of NF-B, AP-1, and heat shock factor protein 1 transcription factors, classically known to signal inflammatory gene expression.…”

Epigenetic reprogramming in the germline: towards the ground state of the epigenome

“…One of the hallmarks of the PGCs undergoing reprogramming is a transient loss of linker H1 histones [23]. In this context, PARP1 has been shown not only to replace H1 in the chromatin, but experimental evidence also shows that H1 is one of the preferred targets of PARP1 ribosylation activity and intensive ribosylation can potentially contribute to the removal/eviction of histones from the chromatin [36][37][38]. The connection between pronounced changes in chromatin compaction and the activation of PARP1 has been previously reported during the heat shock-driven transcriptional activation or in the course of DNA repair.…”