Background: There are seven histone H1 variants in somatic mammalian cells, two of which are replication-independent, H1.0 and H1X. Results: In breast cancer cells, H1.0 is enriched at nucleolus-associated domains, whereas H1X is associated with RNA polymerase II-enriched regions. Conclusion: Most H1 variants show great redundancy across the genome, but there is also some specificity. Significance: Some H1 variants may have specific functions.Unlike core histones, the linker histone H1 family is more evolutionarily diverse, and many organisms have multiple H1 variants or subtypes. In mammals, the H1 family includes seven somatic H1 variants; H1.1 to H1.5 are expressed in a replicationdependent manner, whereas H1.0 and H1X are replication-independent. Using ChIP-sequencing data and cell fractionation, we have compared the genomic distribution of H1.0 and H1X in human breast cancer cells, in which we previously observed differential distribution of H1.2 compared with the other subtypes. We have found H1.0 to be enriched at nucleolus-associated DNA repeats and chromatin domains, whereas H1X is associated with coding regions, RNA polymerase II-enriched regions, and hypomethylated CpG islands. Further, H1X accumulates within constitutive or included exons and retained introns and toward the 3 end of expressed genes. Inducible H1X knockdown does not affect cell proliferation but dysregulates a subset of genes related to cell movement and transport. In H1X-depleted cells, the promoters of up-regulated genes are not occupied specifically by this variant, have a lower than average H1 content, and, unexpectedly, do not form an H1 valley upon induction. We conclude that H1 variants are not distributed evenly across the genome and may participate with some specificity in chromatin domain organization or gene regulation.There are five major classes of histones that participate in the correct folding of eukaryotic DNA into chromatin: the core histones H2A, H2B, H3, and H4, which form an octamer and constitute the nucleosome core particle, and the linker histone H1, which binds to the nucleosomes near the entry/exit sites of linker DNA. Stabilization of the condensed states of chromatin is the function most commonly attributed to the linker histone (1, 2), in addition to its inhibitory effect in vitro on nucleosome mobility (3) and transcription (4).Histone H1 in humans is a family of closely related, single gene-encoded proteins, including seven somatic subtypes (H1.1 to H1.5, H1.0, and H1X), three testis-specific variants (H1t, H1T2, and HILS1), and one restricted to oocytes (H1oo) (5, 6). Among the somatic histone H1 variants, H1.1 to H1.5 are expressed in a replication-dependent manner, whereas H1.0 and H1X are replication-independent. The H1.1 to H1.5-encoding genes are clustered in a region of chromosome 6 together with the core histone genes, whereas the H1X and H1.0 genes are on chromosomes 3 and 22, respectively. H1.2 to H1.5 and H1X are ubiquitously expressed, H1.1 is restricted to certain tissues, and H1.0 accumulat...

Histone H1 has seven variants in human somatic cells and contributes to chromatin compaction and transcriptional regulation. Knock-down (KD) of each H1 variant in breast cancer cells results in altered gene expression and proliferation differently in a variant specific manner with H1.2 and H1.4 KDs being most deleterious. Here we show combined depletion of H1.2 and H1.4 has a strong deleterious effect resulting in a strong interferon (IFN) response, as evidenced by an up-regulation of many IFN-stimulated genes (ISGs) not seen in individual nor in other combinations of H1 variant KDs. Although H1 participates to repress ISG promoters, IFN activation upon H1.2 and H1.4 KD is mainly generated through the activation of the IFN response by cytosolic nucleic acid receptors and IFN synthesis, and without changes in histone modifications at induced ISG promoters. H1.2 and H1.4 co-KD also promotes the appearance of accessibility sites genome wide and, particularly, at satellites and other repeats. The IFN response may be triggered by the expression of noncoding RNA generated from heterochromatic repeats or endogenous retroviruses upon H1 KD. In conclusion, redundant H1-mediated silencing of heterochromatin is important to maintain cell homeostasis and to avoid an unspecific IFN response.

a b s t r a c tIn mammals, the linker histone H1, involved in DNA packaging into chromatin, is represented by a family of variants. H1 tails undergo post-translational modifications (PTMs) that can be detected by mass spectrometry. We developed antibodies to analyze several of these as yet unexplored PTMs including the combination of H1.4 K26 acetylation or trimethylation and S27 phosphorylation. H1.2-T165 phosphorylation was detected at S and G2/M phases of the cell cycle and was dispensable for chromatin binding and cell proliferation; while the H1.4-K26 residue was essential for proper cell cycle progression. We conclude that histone H1 PTMs are dynamic over the cell cycle and that the recognition of modified lysines may be affected by phosphorylation of adjacent residues.

The antioxidant activity of food compounds is one of the properties generating the most interest, due to its health benefits and correlation with the prevention of chronic disease. This activity is usually measured using in vitro assays, which cannot predict in vivo effects or mechanisms of action. The objective of this study was to evaluate the in vivo protective effects of six phenolic compounds (naringenin, apigenin, rutin, oleuropein, chlorogenic acid, and curcumin) and three carotenoids (lycopene B, β-carotene, and astaxanthin) naturally present in foods using a zebrafish embryo model. The zebrafish embryo was pretreated with each of the nine antioxidant compounds and then exposed to tert-butyl hydroperoxide (tBOOH), a known inducer of oxidative stress in zebrafish. Significant differences were determined by comparing the concentration-response of the tBOOH induced lethality and dysmorphogenesis against the pretreated embryos with the antioxidant compounds. A protective effect of each compound, except β-carotene, against oxidative-stress-induced lethality was found. Furthermore, apigenin, rutin, and curcumin also showed protective effects against dysmorphogenesis. On the other hand, β-carotene exhibited increased lethality and dysmorphogenesis compared to the tBOOH treatment alone.