Chromatin states at ribosomal DNA loci

Hamperl, Stephan; Wittner, Manuel; Babl, Virginia; Pérez-Fernández, Jorge; Tschochner, Herbert; Griesenbeck, Joachim

doi:10.1016/j.bbagrm.2012.12.007

Cited by 60 publications

(54 citation statements)

References 160 publications

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“…Unlike most promoters where H3 K4me3 represents an active state, H3 K4me3 at the rDNA promoter denotes a poised state, whereas H3 K4me2 with acetylated H4 represents the active state (16,42). SHPRH is enriched at the rDNA promoter and released from it on starvation.…”

Section: Resultsmentioning

confidence: 99%

SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner

Lee

Park

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Many DNA repair proteins have additional functions other than their roles in DNA repair. In addition to catalyzing PCNA polyubiquitylation in response to the stalling of DNA replication, SHPRH has the additional function of facilitating rRNA transcription by localizing to the ribosomal DNA (rDNA) promoter in the nucleoli. SHPRH was recruited to the rDNA promoter using its plant homeodomain (PHD), which interacts with histone H3 when the fourth lysine of H3 is not trimethylated. SHPRH enrichment at the rDNA promoter was inhibited by cell starvation, by treatment with actinomycin D or rapamycin, or by depletion of CHD4. SHPRH also physically interacted with the RNA polymerase I complex. Taken together, we provide evidence that SHPRH functions in rRNA transcription through its interaction with histone H3 in a mammalian target of rapamycin (mTOR)-dependent manner.SHPRH | rRNA transcription | histone H3 methylation | mTOR H uman ribosomal DNA (rDNA) is composed of hundreds of tandem repeats of 42.9-kb rDNA units that are organized into transcribed and intergenic regions (1). About one-half the 47S precursor ribosomal RNA (pre-rRNA) genes are actively transcribed, and the other half remain silent (2, 3). Transcription, processing of rRNA, and the assembly of ribosomes take place in the nucleoli (2, 4). Once transcribed in the nucleoli, pre-rRNA is immediately processed into small mature 28S, 18S, and 5.8S rRNAs that, together with ribosomal proteins, make a ribosome. Tight regulation of ribosome biogenesis, including rRNA transcription and synthesis of ribosomal proteins, is important in many biological processes such as cell proliferation, apoptosis, and autophagy (5-7), and is closely associated with metabolic processes. Because of its importance in many metabolic pathways, dysregulation of ribosomal biogenesis is linked to aging and diverse diseases, including anemia and cancers (8-12). 47S pre-rRNA is transcribed by the RNA polymerase I complex, whose activity is controlled by cellular responses to nutritional states, cellular stresses, growth, differentiation, and cell cycle (9). Posttranslational modifications of transcription factors, for example, phosphorylation of upstream binding factor (UBF), help regulate rRNA transcription (13). In addition to posttranslational modifications of transcription factors, nucleolar remodeling complex, NuRD (nucleosome remodeling and deacetylation) complex, and energy-dependent nucleolar silencing complex also affect rRNA transcription by modifying epigenetic signatures of rDNA, as well as histones in the rDNA promoter (14-16). In addition to conventional active and silent histone signatures, the rDNA promoter has another histone signature called a poised state. CHD4 and CSB-containing NuRD complex establish a poised chromatin signature of rDNA that represses but primes rRNA transcription by marking histone H3 with both active (H3 K4me3) and inactive (H3 K27me3) modifications (16). However, it is unclear how these epigenetic changes control the transcription of rRNA.The mammali...

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Section: Resultsmentioning

confidence: 99%

SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner

Lee

Park

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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“…WT mouse embryo fibroblasts (PMEF-CFL, lot 2137256-1) were from Millipore (Billerica, MA). Cells were cultured in Iscove's modified Dulbecco's medium containing 10% fetal bovine serum, antibiotics (100 g of penicillin and 50 g of streptomycin sulfate/ml), and 2 mM glutamine at 37°C, 5% CO 2 .…”

Section: Methodsmentioning

confidence: 99%

Loss of Nucleolar Histone Chaperone NPM1 Triggers Rearrangement of Heterochromatin and Synergizes with a Deficiency in DNA Methyltransferase DNMT3A to Drive Ribosomal DNA Transcription

Olausson

Nistér

Lindström

2014

Journal of Biological Chemistry

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Background: NPM1 is a nucleolar histone chaperone mutated in cancer. Results: NPM1-deficient cells display rearrangement of perinucleolar heterochromatin, and simultaneous knockdown of NPM1 and DNMT3A enhances transcription of ribosomal DNA. Conclusion: NPM1 loss disrupts heterochromatin organization around the nucleolus. Significance: Rearrangement of heterochromatin in NPM1-deficient cells may be of importance in tumor development.

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“…Genes transcribed by RNA polymerase I (mainly, ribosomal genes) are present in mul ple copies per genome, but only a frac on of them is ac vely transcribed at a given moment. The chroma n in the ribosomal gene loci may exist in different states -"open" state, typical of transcribed genes or a "closed" state, ghtly packed in nucleosomes [1405,1406]. In 2012 it was experimentally proven that NER was more efficient in non-packed than in packed ribosomal DNA [246,247].…”

Section: S Snegov the Experiments Of Professor Bran Ng (1977)mentioning

confidence: 99%

DNA repair systems

Chakarov¹,

Petkova²,

Russev³

2014

Biodiscovery

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This paper provides detailed insight into the mechanisms of repair of different types of DNA damage and the direct molecular players (enzymes repairing the damage or tagging the damaged site for further processing; damage sensor molecules; other signalling and effector molecules). The gene c bases of diseases and condi ons associated with defec ve DNA repair are comprehensively reviewed, from the 'classic' severe diseases such as xeroderma pigmentosum and Cockayne syndrome to the much more subtle UV sensi vity syndromes. The review analyses the basic molecular mechanisms underlying the rela vely rare monogenic diseases of DNA repair and management of genome integrity as well as the common mul factorial diseases and condi ons with late onset that are associated with increased levels of oxida ve stress (metabolic syndrome, diabetes type 2, cardiovascular disease) and with accumula on of 'errors' in DNA (normal and pathological ageing phenotypes, various cancers). The role of cell cycle checkpoints in dividing cells and the mechanisms of decision-making for the fate of a damaged cell are discussed with regards to the cell homeostasis in normal and cancerous ssues. The role of major DNA damageassociated signalling and effector molecules (p53, ATM, poly-(ADP-ribose)-polymerase, DNA-dependent protein kinase, BRCA proteins, re noblastoma protein, and others) is discussed and illustrated with examples in the context of health and disease. DNA repair and programmed cell death are viewed together as a unified mechanism for limi ng the presence of damaged cells and cells with poten ally oncogenic transforma on in mul cellular organisms. Special a en on is paid to ageing as a natural phenomenon and an adap ve evolu onary mechanism, with a brief outline of 'successful ageing'. The differen al rates of repair of DNA in transcribed and nontranscribed regions of the genome and the specifici es of DNA repair profile in some types of cells (terminally differen ated cells, pluripotent stem cells, etc.) and in certain taxonomic groups (e.g. 'the rodent repairadox') are discussed with regards to replica ve ageing and the evolu onary processes on microand macroscale. The role of mutagenesis as a 'hit and miss' mechanism and the 'leakiness' of DNA repair for increasing gene c diversity in the course of individual life and on evolu onary scale and the phenomenology of ongoing molecular evolu on are extensively reviewed. Conflict of Interests:No poten al conflict of interest was disclosed by any of the authors. Types of DNA repair systemsIf you wish for peace, prepare for war.Publius Flavius Vege us Renatus, De Re Militari (circa 380 AD).DNA damage is a very broad term, encompassing many different types of lesions in DNA.Accordingly, DNA repair comprises many different types of pathways and mechanisms covering virtually every possible type of injury to the sequence or the structure of DNA.Accep ng Lewin's defini on of DNA damage "... any change that introduces a devia on from the usual double-helical structure" [1] , we may pre...

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Chromatin states at ribosomal DNA loci

Cited by 60 publications

References 160 publications

SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner

SHPRH regulates rRNA transcription by recognizing the histone code in an mTOR-dependent manner

Loss of Nucleolar Histone Chaperone NPM1 Triggers Rearrangement of Heterochromatin and Synergizes with a Deficiency in DNA Methyltransferase DNMT3A to Drive Ribosomal DNA Transcription

DNA repair systems

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