Heterochromatin and<i>tri</i>-methylated lysine 20 of histone H4 in animals

Kourmouli, Niki; Jeppesen, Peter; Mahadevhaiah, Shantha; Burgoyne, Paul S.; Wu, Renbiao; Gilbert, David M.; Bongiorni, Silvia; Prantera, Giorgio; Fanti, Laura; Pimpinelli, Sergio; Wei, Shi; Fundele, Reinald; Singh, Prim B.

doi:10.1242/jcs.01238

Cited by 225 publications

(194 citation statements)

References 51 publications

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“…Emerging evidence provided links between histone H4-Lys 20 trimethylation and oncotransformation (24,30,46,47). Interestingly, Fraga et al (24) have observed a decrease in trimethylated histone H4-Lys 20 in leukemia cell lines when compared with normal lymphocytes.…”

Section: Discussionmentioning

confidence: 99%

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Fractionated Low-Dose Radiation Exposure Leads to Accumulation of DNA Damage and Profound Alterations in DNA and Histone Methylation in the Murine Thymus

Pogribny

Koturbash

Tryndyak

et al. 2005

Molecular Cancer Research

149

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Thymus, an important component of hematopoietic tissue, is a well-documented ''target'' of radiation carcinogenesis. Both acute and fractionated irradiation result in a high risk of leukemia and thymic lymphoma. However, the exact mechanisms underlying radiation-induced predisposition to leukemia and lymphoma are still unknown, and the contributions of genetic and epigenetic mechanisms in particular have yet to be defined. Global DNA hypomethylation is a well-known characteristic of cancer cells. Recent studies have also shown that tumor cells undergo prominent changes in histone methylation, particularly a substantial loss of trimethylation of histone H4-Lys 20 and demethylation of genomic DNA. These losses are considered a universal marker of malignant transformation. In the present study, we investigated the effect of low-dose radiation exposure on the accumulation of DNA lesions and alterations of DNA methylation and histone H4-Lys 20 trimethylation in the thymus tissue using an in vivo murine model. For the first time, we show that fractionated whole-body application of 0.5 Gy X-ray leads to decrease in histone H4-Lys 20 trimethylation in the thymus. The loss of histone H4-Lys 20 trimethylation was accompanied by a significant decrease in global DNA methylation as well as the accumulation of DNA damage as monitored by persistence of histone ;H2AX foci in the thymus tissue of mice exposed to fractionated irradiation. Altered DNA methylation was associated with reduced expression of maintenance (DNMT1) and, to a lesser extent, de novo DNA methyltransferase DNMT3a in exposed animals. Expression of another de novo DNA methyltransferase DNMT3b was decreased only in males. Irradiation also resulted in f20% reduction in the levels of methyl-binding proteins MeCP2 and MBD2. Our results show the involvement of epigenetic alterations in radiation-induced responses in vivo. These changes may play a role in genome destabilization that ultimately leads to cancer. (Mol Cancer Res 2005;3(10):553 -61)

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Section: Discussionmentioning

confidence: 99%

“…Recent studies have shown that loss of histone H4-Lys 20 trimethylation could result in a more ''relaxed'' heterochromatin organization, which markedly impairs genome stability and viability of the cells (46,47) and may lead to the malignant transformation (24).…”

Section: Radiation-induced Changes In Histone H4-lys 20 Trimethylationmentioning

confidence: 99%

Fractionated Low-Dose Radiation Exposure Leads to Accumulation of DNA Damage and Profound Alterations in DNA and Histone Methylation in the Murine Thymus

Pogribny

Koturbash

Tryndyak

et al. 2005

Molecular Cancer Research

149

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“…4E). (31) In addition, H4-K20 can be monomethylated or trimethylated by the HMTs PR-Set7 (21,32) and Suv4-20h1/2 (33) respectively (Fig. 4F,G).…”

Section: Histone Methyltransferasesmentioning

confidence: 99%

“…(21,26,32) However, the mechanisms behind this so-called ''epigenetic crosstalk'' have yet to be fully determined. Histone methylation could also be more of a lasting covalent modification than histone deacetylation.…”

Section: Histone Methyltransferasesmentioning

confidence: 99%

Heterochromatin?many flavours, common themes

Craig

2004

Bioessays

115

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SummaryHeterochromatin remains condensed throughout the cell cycle, is generally transcriptionally inert and is built and maintained by groups of factors with each group member sharing a similar function. In mammals, these groups include sequence-specific transcriptional repressors, functional RNA and proteins involved in DNA and histone methylation. Heterochromatin is cemented together via interactions within and between each protein group and is maintained by the cell's replication machinery. It can be constitutive (permanent) or facultative (developmentally regulated) and be any size, from a gene promotor to a whole genome. By studying the formation of facultative heterochromatin, we have gained information about how heterochromatin is assembled. We have discovered that there are many different architectural plans for the building of heterochromatin, leading to a seemingly never-ending variety of heterochromatic loci, with each built according to a general rule.

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“…This reduces autophagy, thereby providing a feedback mechanism to control the amount of autophagy [17]. Furthermore, global changes in H4K20me3 [19], H3K4me3 [17], and H3K56ac [20] have been associated with autophagy induction, but whether and how this affects autophagy remains to be determined [17,19,20]. Importantly, extensive studies which assess and combine genome-wide transcriptomic and epigenomic events underlying autophagy are lacking.…”

Section: Introductionmentioning

confidence: 99%

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

et al. 2018

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Macroautophagy (hereafter autophagy) is a lysosomal degradation pathway critical for maintaining cellular homeostasis and viability, and is predominantly regarded as a rapid and dynamic cytoplasmic process. To increase our understanding of the transcriptional and epigenetic events associated with autophagy, we performed extensive genome-wide transcriptomic and epigenomic profiling after nutrient deprivation in human autophagy-proficient and autophagy-deficient cells. We observed that nutrient deprivation leads to the transcriptional induction of numerous autophagy-associated genes. These transcriptional changes are reflected at the epigenetic level (H3K4me3, H3K27ac, and H3K56ac) and are independent of autophagic flux. As a proof of principle that this resource can be used to identify novel autophagy regulators, we followed up on one identified target: EGR1 (early growth response 1), which indeed appears to be a central transcriptional regulator of autophagy by affecting autophagy-associated gene expression and autophagic flux. Taken together, these data stress the relevance of transcriptional and epigenetic regulation of autophagy and can be used as a resource to identify (novel) factors involved in autophagy regulation.

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Heterochromatin andtri-methylated lysine 20 of histone H4 in animals

Cited by 225 publications

References 51 publications

Fractionated Low-Dose Radiation Exposure Leads to Accumulation of DNA Damage and Profound Alterations in DNA and Histone Methylation in the Murine Thymus

Fractionated Low-Dose Radiation Exposure Leads to Accumulation of DNA Damage and Profound Alterations in DNA and Histone Methylation in the Murine Thymus

Heterochromatin?many flavours, common themes

Transcriptional and epigenetic profiling of nutrient-deprived cells to identify novel regulators of autophagy

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