The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin

Giri, Sumanprava; Aggarwal, Vasudha; Pontis, Julien; Shen, Zhen; Chakraborty, Arindam; Khan, Abid; Mizzen, Craig A.; Prasanth, Kannanganattu V.; Ait‐Si‐Ali, Slimane; Ha, Taekjip; Prasanth, Supriya G.

doi:10.7554/elife.06496

Cited by 38 publications

(64 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, it is likely that the chromatin landscape of the X chromosome is still altered, relative to the rest of the genome when H3K9me2/me3 levels are perturbed and this altered epigenome may define late replication in Caenorhabditis. In mammals, prereplication complex-associated protein ORCA/LRWD1 has been shown to specifically recruit H3K9 methyltransferases and be important for late replication (Giri et al 2015). However, no orthologs of ORCA/LRWD1 are present in the annotated Caenorhabditis genomes.…”

Section: Why Meiotic Silencing In Caenorhabditis?mentioning

confidence: 99%

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Larson

Van

Nakayama³

et al. 2016

Genetics

View full text Add to dashboard Cite

During meiosis in the heterogametic sex in some species, sex chromosomes undergo meiotic sex chromosome inactivation (MSCI), which results in acquisition of repressive chromatin and transcriptional silencing. In Caenorhabditis elegans, MSCI is mediated by MET-2 methyltransferase deposition of histone H3 lysine 9 dimethylation. Here we examined the meiotic chromatin landscape in germ lines of four Caenorhabditis species; C. remanei and C. brenneri represent ancestral gonochorism, while C. briggsae and C. elegans are two lineages that independently evolved hermaphroditism. While MSCI is conserved across all four species, repressive chromatin modifications are distinct and do not correlate with reproductive mode. In contrast to C. elegans and C. remanei germ cells where X chromosomes are enriched for histone H3 lysine 9 dimethylation, X chromosomes in C. briggsae and C. brenneri germ cells are enriched for histone H3 lysine 9 trimethylation. Inactivation of C. briggsae MET-2 resulted in germ-line X chromosome transcription and checkpoint activation. Further, both histone H3 lysine 9 di-and trimethylation were reduced in Cbr-met-2 mutant germ lines, suggesting that in contrast to C. elegans, H3 lysine 9 di-and trimethylation are interdependent. C. briggsae H3 lysine 9 trimethylation was redistributed in the presence of asynapsed chromosomes in a sex-specific manner in the related process of meiotic silencing of unsynapsed chromatin. However, these repressive marks did not influence X chromosome replication timing. Examination of additional Caenorhabditis species revealed diverse H3 lysine 9 methylation patterns on the X, suggesting that the sex chromosome epigenome evolves rapidly.

show abstract

Section: Why Meiotic Silencing In Caenorhabditis?mentioning

confidence: 99%

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Larson

Van

Nakayama³

et al. 2016

Genetics

View full text Add to dashboard Cite

show abstract

“…This role in the initiation of replication is likely to be conserved in mammals because human HP1 interacts with hexa-meric ORC through ORC subunits ORC1 or 3, and these interactions are mutually re-enforcing (Prasanth et al 2010). The interaction of ORC with HP1-containing heterochromatin is stabilized by an ORC-associated protein, ORC-A, that binds to H3K9me2 and H3K9me3 and recruits a HMTase mega-complex containing SETDB1, G9a, GLP and SUV39H1 (Fritsch et al 2010), which generates H3K9me3 at the origin of replication (Giri et al 2015). After initiation, the next stages include the assembly and activation of the replicative helicase and processivity of the replicative polymerases.…”

Section: Replication Of Heterochromatin-like Domains and Complexesmentioning

confidence: 99%

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

Singh

2016

J Biosci

View full text Add to dashboard Cite

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatinlike complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed.[Singh PB 2016 Heterochromatin and the molecular mechanisms of 'parent-of-origin' effects in animals. J. Biosci.] http://www.ias.ac.in/jbiosci J. Biosci. * Indian Academy of Sciences DOI: 10.1007/s12038-016-9650-9Keywords. Epigenetics; genomic imprinting; heterochromatin; HP1; KRAB-ZFP Abbreviations used: 5hmC, 5-hydroxymethylcytosine; 5mC, 5-methylcytosine; ADD, ATRX-DNMT3-DNMT3L domain; ATRX, Alpha Thalassemia/Mental Retardation Syndrome X-Linked; CAF-1, chromatin assembly factor 1; CD, chromodomain; CE, controlling element; CF, chromocenter formation; CGIs, CpG islands; CSD, chromo shadow domain; DamID, DNA adenine methyltransferase identification; DAXX, Death Domain associated protein; DNMT1, maintenance DNA methyltransferase 1; DNMT3A, de novo DNA methyltransferase 3A; DNMT3B, de novo DNA methyltransferase 3B; DNMT3L, DNA methyltransferase 3L; ES, embryonic stem; G9a, K9H3 HMTase; GLP, G9a-like protein K9H3 HMTase; gDMRs, germline differentially methylated regions; H3K9me2, di-methylated lysine 9 on histone H3; H3K9me3, tri-methylated lysine 9 on histone H3; H3S10P, phosphorylation of serine 10 on histone H3; H4K20me3, tri-methylated lysine 20 on histone

show abstract

“…There have been recent reports suggesting a requirement of Ehmt2 for genome integrity. 81,89 How a loss of Ehmt2 dependant methylation leads to chromosome instability is still not well understood; One intriguing possibility is suggested in the recent report that Ehmt2 participates in a multi-HMT complex that is required for maintaining pericentromeric chromatin, [90][91][92] a structure that is essential for proper spindle attachment and chromosome segregation during mitosis (reviewed in ref. 93).…”

Section: Emerging Roles Of Ehmt2mentioning

confidence: 99%

The expanding role of the Ehmt2/G9a complex in neurodevelopment

2017

View full text Add to dashboard Cite

Epigenetic regulators play a crucial role in neurodevelopment. One such epigenetic complex, Ehmt1/2 (G9a/GLP), is essential for repressing gene transcription by methylating H3K9 in a highly tissue-and temporal-specific manner. Recently, data has emerged suggesting that this complex plays additional roles in regulating the activity of numerous other non-histone proteins. While much is known about the downstream effects of Ehmt1/2 function, evidence is only beginning to come to light suggesting the control of Ehmt1/2 function may be, at least in part, due to context-dependent binding partners. Here we review emerging roles for the Ehmt1/2 complex suggesting that it may play a much larger role than previously recognized, and discuss binding partners that we and others have recently characterized which act to coordinate its activity during early neurodevelopment.

show abstract

The preRC protein ORCA organizes heterochromatin by assembling histone H3 lysine 9 methyltransferases on chromatin

Cited by 38 publications

References 58 publications

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Plasticity in the Meiotic Epigenetic Landscape of Sex Chromosomes inCaenorhabditisSpecies

Heterochromatin and the molecular mechanisms of ‘parent-of-origin’ effects in animals

The expanding role of the Ehmt2/G9a complex in neurodevelopment

Contact Info

Product

Resources

About