Histone H1 Depletion in Mammals Alters Global Chromatin Structure but Causes Specific Changes in Gene Regulation

Fan, Yuhong; Nikitina, Tatiana; Zhao, Jie; Fleury, Tomara J.; Bhattacharyya, Riddhi; Bouhassira, Eric E.; Stein, Arnold; Woodcock, Christopher L.; Skoultchi, Arthur I.

doi:10.1016/j.cell.2005.10.028

Cited by 502 publications

(666 citation statements)

References 62 publications

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“…(iii) DNMT3B7 may affect DNA methylation as outlined above, which could in turn lead to alterations in histone modifications. Mice lacking histone H1 showed alterations in DNA methylation levels and consequent gene expression changes in relatively few genes, often in imprinted genes or genes located on the X chromosome (Fan et al, 2005). In addition, histone H3 and H4 acetylation levels increased after patients received 5-azacytidine, a global hypomethylating agent (Gore et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

et al. 2007

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Cancer cells display an altered distribution of DNA methylation relative to normal cells. Certain tumor suppressor gene promoters are hypermethylated and transcriptionally inactivated, whereas repetitive DNA is hypomethylated and transcriptionally active. Little is understood about how the abnormal DNA methylation patterns of cancer cells are established and maintained. Here, we identify over 20 DNMT3B transcripts from many cancer cell lines and primary acute leukemia cells that contain aberrant splicing at the 5 0 end of the gene, encoding truncated proteins lacking the C-terminal catalytic domain. Many of these aberrant transcripts retain intron sequences. Although the aberrant transcripts represent a minority of the DNMT3B transcripts present, Western blot analysis demonstrates truncated DNMT3B isoforms in the nuclear protein extracts of cancer cells. To test if expression of a truncated DNMT3B protein could alter the DNA methylation patterns within cells, we expressed DNMT3B7, the most frequently expressed aberrant transcript, in 293 cells. DNMT3B7-expressing 293 cells have altered gene expression as identified by microarray analysis. Some of these changes in gene expression correlate with altered DNA methylation of corresponding CpG islands. These results suggest that truncated DNMT3B proteins could play a role in the abnormal distribution of DNA methylation found in cancer cells.

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Section: Discussionmentioning

confidence: 99%

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

et al. 2007

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“…The participation of different histone H1 subtypes in these processes is not fully elucidated (6). It has been shown that embryonic histone H1 is vital for correct chromosome segregation in Xenopus egg extracts (27).…”

Section: Discussionmentioning

confidence: 99%

“…The binding of H1 proteins to chromatin is highly dynamic (4,5). Histone H1 stabilizes the nucleosome and is important in compaction of chromatin into higher order structures (6,7). Moreover, it has been implicated in transcriptional regulation (8).…”

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Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

et al. 2010

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Histone H1 is an important constituent of chromatin, which undergoes major structural rearrangements during mitosis. However, the role of H1, multiple H1 subtypes, and H1 phosphorylation is still unclear. In normal human fibroblasts, phosphorylated H1 was found located in nuclei during prophase and in both cytoplasm and condensed chromosomes during metaphase, anaphase, and telophase as detected by immunocytochemistry. Moreover, we detected remarkable differences in the distribution of the histone H1 subtypes H1.2, H1.3, and H1.5 during mitosis. H1.2 was found in chromatin during prophase and almost solely in the cytoplasm of metaphase and early anaphase cells. In late anaphase, it appeared in both chromatin and cytoplasm and again in chromatin during telophase. H1.5 distribution pattern resembled that of H1.2, but H1.5 was partitioned between chromatin and cytoplasm during metaphase and early anaphase. H1.3 was detected in chromatin in all cell cycle phases. We propose therefore, that H1 subtype translocation during mitosis is controlled by phosphorylation, in combination with H1 subtype inherent affinity. We conclude that H1 subtypes, or their phosphorylated forms, may leave chromatin in a regulated way to give access for chromatin condensing factors or transcriptional regulators during mitosis. ' 2010International Society for Advancement of Cytometry Key terms histone H1; chromatin; cell cycle; mitosis IN the cell cycle, DNA and protein content are duplicated, and the cell divides in two in a strict sequential order of events. During prophase, the replicated chromosomes condense, and the nuclear membrane breaks down in prometaphase. At metaphase, the chromosomes are aligned at the equator of the mitotic spindle, and the sister chromatids are segregated to the two poles of the spindle during anaphase. Finally, the separation is completed during telophase by cytoplasmic division. Impaired cell cycle control or cell cycle progression may result in cell death or malignant transformation.

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“…Several knockout studies across a wide range of organisms revealed that H1 has multiple functions, including participation in the regulation of most nuclear processes (Izzo et al 2008;Happel and Doenecke 2009), mediated at least in some cases by specific H1-protein interactions (McBryant et al 2010). H1 depletion leads to perturbation in the expression of only a subset of genes, with both up-regulation and down-regulation (Shen and Gorovsky 1996;Hellauer et al 2001;Fan et al 2005). This suggests that in vivo, rather than being simply a global repressor, H1 can act as a fine tuner of gene expression.…”

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confidence: 99%

A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation

Kamieniarz¹,

Izzo²,

Dundr³

et al. 2012

Genes Dev.

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The linker histone H1 is a key player in chromatin organization, yet our understanding of the regulation of H1 functions by post-translational modifications is very limited. We provide here the first functional characterization of H1 acetylation. We show that H1.4K34 acetylation (H1.4K34ac) is mediated by GCN5 and is preferentially enriched at promoters of active genes, where it stimulates transcription by increasing H1 mobility and recruiting a general transcription factor. H1.4K34ac is dynamic during spermatogenesis and marks undifferentiated cells such as induced pluripotent stem (iPS) cells and testicular germ cell tumors. We propose a model for H1.4K34ac as a novel regulator of chromatin function with a dual role in transcriptional activation.

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Histone H1 Depletion in Mammals Alters Global Chromatin Structure but Causes Specific Changes in Gene Regulation

Cited by 502 publications

References 62 publications

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

Cancer cells express aberrant DNMT3B transcripts encoding truncated proteins

Translocation of histone H1 subtypes between chromatin and cytoplasm during mitosis in normal human fibroblasts

A dual role of linker histone H1.4 Lys 34 acetylation in transcriptional activation

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