Cell cycle-dependent accumulation of histone H3.3 and euchromatic histone modifications in pericentromeric heterochromatin in response to a decrease in DNA methylation levels

Basic concepts of epigenetics

“…155 DNA methylation within heterochromatin must be sustained, as its loss could initiate the dismantlement of chromatin, acetylation of histone H4, and H3K4 di-and trimethylation, all events associated with relaxation of nucleosomes. 156 The nuclear lamina is required to lock the peripheral position of heterochromatin within the methyl-CpG-binding domain (MBD) protein 1; MBD2, methylCpG-binding domain (MBD) protein 2; MBD3, methyl-CpGbinding domain (MBD) protein 3; MBD4, methyl-CpG-binding domain (MBD) protein 4; MBPs, methyl-CpG binding proteins; MCAF1, MBD1-containing chromatin associated factor; MeCP2, methyl-CpG-binding protein; Mi2-NuRD, Mi-2/ nucleosome remodeling and histone de-acetylation chromatin remodeling complex miRNAs, microRNA; mRNA, messenger RNA; MSK1, mitogen-and stress-activated protein kinase 1; MTA1-like, metastasis associated 1-like; MTA2, metastasis associated 2; NAP-1, nucleosome assembly protein-1; NBDs, nucleosomal binding domains; N-CoR1, nuclear receptor co-repressor 1; NE, nuclear envelope; NuRD, nucleosome remodeling and deacetylation; NURF, nucleosome remodeling factor; ORC2, origin recognition complex protein; PAH, paired amphipathic helix; PCAF, p300 cAhlP response element binding protein CREBI-binding protein associated factor; PHD, plant homeo domain-zinc finger domains; RNP II, RNA polymerase II; pre-SET/SET, histone lysine methyltransferases; PRMT5, histonearginine N-methyltransferase 5; P-TEFb, positive transcription elongation factor b; PWWP, proline-tryptophan-tryptophanproline domain; RbAp48/p46, Rb-associated histone deacetylase complex; RP58, repression protein of 58 kDa; SAP18, Sin3A-associated protein, 18 kDa; SAP30, Sin3A-associated protein, 30 kDa; SET, su(var)39, enhancer of zeste, trithorax domains; SETDB1, SET domain bifurcated 1; SETDB1/Suv39 h1, histone methyltransferase; Sin3, transcriptional co-repressor Sin3; Sin3A, SIN3 homolog A, transcription regulator (yeast); Sin3B, SIN3 homolog B, transcription regulator (yeast); SIRT, silent information regulator 2; SMARC, SWI/SNF related, matrix associated, actin dependent regulator of chromatin; SMARCA4, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; SNF, sucrose non fermenting; Sp100, SP100 nuclear antigen; Sp110, SP110 nuclear body protein; Sp140, SP140 nuclear body protein; SRA, SET and RING associated; SRCAP, SNF2-related CBP activator protein; SUN, Sad1 and UNC84 domain containing 1; Suv39 h1, suppressor called variegation 3-9 homologue 1; SWI/SNF, SWItch/ sucrose non fermentable yeast nucleosome remodeling complex; TAF1, TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor; TFIIB, general transcription factor IIB; TIP48, components of the histone acetylase/chromatin remodeling complex; TIP5, termination factor TTFI-interacting protein 5; Tip60, K(lysine) acetyltransferase 5; Tpase, thymidine phosphorylase; TRAP220, thyroid receptor-associated protein complex 220; TRDs, transcriptional repressor domains; TRIP12, thyroid hormone receptor interactor 12; TRRAP, transformation/transcription domain-associated protein; UHRF1, ubiquitin-like with PHD and ring finger domains 1; USP7, ubiquitin specific peptidase 7 (herpes virus-associated); WD40, beta-transducin repeat; ZBTB38, zinc finger and BTB domain containing 38; ZBTB4, zinc finger and BTB domain containing 4 the transmittance of epigenetic information is heritable through mitosis and meiosis. While this describes a very basic model, the complexities of epigenetic control in regulating the phenotype seem infinite.…”

Pericentric heterochromatin state during the cell cycle controls the histone variant composition of centromeres

“…Furthermore, increased transcription of major satellite repeats occurred in both cases (supplementary material Fig. S2F) (Eymery et al, 2009;Lehnertz et al, 2003;Sugimura et al, 2010), with more pronounced changes in 5-Aza-treated relative to untreated cells than in Suv39h dnMEFs relative to wild-type MEFs. It is also important to note that whereas Suv39h dnMEFs represent a system that has adapted to the heterochromatin perturbations during several cell generations, 5-Aza-treated fibroblasts show an acute response to changes in PHC state.…”

“…Importantly, whereas 5-Aza-treated cells retained typical heterochromatic marks, such as an enrichment of H3K9me3 and HP1a, Suv39h dnMEFs lost these marks (supplementary material Fig. S2D) (Peters et al, 2001;Sugimura et al, 2010;Taddei et al, 2001) but did not display a striking decrease in DNA methylation at PHC (supplementary material Fig. S2E).…”

Sonic Hedgehog Signaling Affected by Promoter Hypermethylation Induces Aberrant Gli2 Expression in Spina Bifida

“…Moreover, hypermethylation is necessary to maintain the status of heterochromatin, which is transcriptionally inactive [1,29]. In our study, the observed reduced methylation in the 5-Aza-treated group of HCT-15 cells was associated with higher chromatin accessibility and increased gli2 expression, suggesting that regulation of the chromatin status is the mechanism by which gli2 transcription is affected by DNA methylation.…”

“…A few key signaling pathways for NTDs have been identified, including noncanonical Wnt signaling (planar cell polarity), sonic hedgehog (Shh), and folate/1-methyl carbon metabolic pathway [1][2][3][4][5]. Though over 200 genes have been found to be involved in the regulation of neural tube closure in animal models, increasing attention is being focused on epigenetic mechanisms in NTDs [6][7][8].…”