Chromatin Modifications and Their Function

“LSD1 acts to demethylate H3K4 and repress transcription (Shi et al., 2004).”

“H3K9 can also be demethylated by JHDM2A (Yamane et al., 2006), JMJD2A/JHDM3A (Tsukada et al., 2006; Whetstine et al., 2006), JMJD2B (Fodor et al., 2006), JMJD2C/GASC1 (Cloos et al., 2006), and JMJD2D (Shin and Janknecht, 2006).”

“In vitro experiments provide a role for H4K16Ac in chromatin decondensation (Shogren-Knaak et al., 2006).”

“In addition, in vivo data demonstrate that mono- (but not di-) methylated arginines can be deiminated (Wang et al., 2004a).”

“Acetyltransferases are divided into three main families, GNAT, MYST, and CBP/p300 (Sterner and Berger, 2000).”

“…are found may specify a preference for nucleosomal verses free histones (Lee et al., 2005a); proteins that associate with the enzyme may affect its selection of residue to modify (Metzger et al., 2005) or the degree of methylation (mono-, di-, or tri-) at a specific site (Steward et al., 2006).”

“Enzymes have been identified for acetylation (Sterner and Berger, 2000), methylation (Zhang and Reinberg, 2006), phosphorylation (Nowak and Corces, 2004), ubiquitination (Shilatifard, 2006), sumoylation (Nathan et al.”

“Limited evidence from mouse and human tissues indicates that this is a conserved characteristic (Bernstein et al., 2005; see Review by B.E. Bernstein et al., page 669 of this issue).”

“Most of the information we have has come from global analyses in budding yeast (Liu et al., 2005; Pokholok et al., 2005).”

“The use of ChIP on CHIP technology revealed that two methylation sites with conflicting output (H3K27me and H3K4me) coexist in these bivalent domains (Azuara et al., 2006; Bernstein et al., 2005).”

“One role for H3K36me is the suppression of inappropriate initiation from cryptic start sites within the coding region (Carrozza et al., 2005; Cuthbert et al., 2004; Joshi and Struhl, 2005; Keogh et al., 2005).”

“Deletion of the enzyme Dicer that prosesses small RNAs can also affect heterochromatin formation, methylation of H3K9, and recruitment of HP1 (Fukagawa, 2004; Kanellopoulou et al., 2005; also see Review by M. Zaratiegui et al., page 763 of this issue).”

“Work in fission yeast has shown that small RNAs are associated with chromatinmodifying complexes and can deliver histone-modifying enzymes to chromatin (Verdel et al., 2004).”

“This recruitment tethers the SNF2L ATPase to activate H0XC8 gene expression (Wysocka et al., 2006; Figure 3A).”

“Enzymes have been identified for acetylation (Sterner and Berger, 2000), methylation (Zhang and Reinberg, 2006), phosphorylation (Nowak and Corces, 2004), ubiquitination (Shilatifard, 2006), sumoylation (Nathan et al.”

“In addition, in vivo data demonstrate that mono- (but not di-) methylated arginines can be deiminated (Wang et al., 2004a).”

“, 2004), recent structural and functional studies suggest that this protein recognizes H4K20 methylation very avidly and is recruited to sites of DNA via H4K20 methylation (Botuyan et al., 2006).”

“Recent data suggest that one of the mechanisms by which H3S10 phosphorylation may function is via the displacement of HP1 from H3K9me, which normally compacts chromatin (Fischle et al., 2005).”

“The PHD-finger protein ING2 tethers the repressive mSin3a-HDAC1 histone deacetylases complex to highly active, proliferation-specific genes after the exposure of cells to DNA-damaging agents (Pena et al., 2006; Shi et al., 2006).”

“Recent work in mice has shown that small RNAs present in sperm can be transmitted to offspring where they mediate an epigenetic phenotype called paramutation, a process first identified in plants (Rassoulzadegan et al., 2006).”

“Although this protein may have some affinity for H3K79 methylation (Huyen et al., 2004), recent structural and functional studies suggest that this protein recognizes H4K20 methylation very avidly and is recruited to sites of DNA via H4K20 methylation (Botuyan et al.”

“H3K9 can also be demethylated by JHDM2A (Yamane et al., 2006), JMJD2A/JHDM3A (Tsukada et al., 2006; Whetstine et al., 2006), JMJD2B (Fodor et al., 2006), JMJD2C/GASC1 (Cloos et al., 2006), and JMJD2D (Shin and Janknecht, 2006).”

“One other protein, WDR5, has been demonstrated to bind H3K4me1 and H3K4me2 (Wysocka et al., 2005).”

“Double-strand breaks mediated by Topoisomerase II b activate the PARP-1 enzyme, which then directs chromatin changes to the estrogen-regulated PS2 gene (Ju et al., 2006).”

“One role for H3K36me is the suppression of inappropriate initiation from cryptic start sites within the coding region (Carrozza et al., 2005; Cuthbert et al., 2004; Joshi and Struhl, 2005; Keogh et al., 2005).”

“Like lysine methylation, arginine methylation can be either activatory or repressive for Cell 128, 693–705, February 23, 2007 ª2007 Elsevier Inc. 699 transcription, and the enzymes (protein arginine methyltransferases, PRMT’s) are recruited to promoters by transcription factors (Lee et al., 2005b).”

“One role for H3K36me is the suppression of inappropriate initiation from cryptic start sites within the coding region (Carrozza et al., 2005; Cuthbert et al., 2004; Joshi and Struhl, 2005; Keogh et al., 2005).”

“Both complexes have a repressive capability for transcription, so their occlusion by positively acting modifications makes sense (Margueron et al., 2005).”

“H3K9 can also be demethylated by JHDM2A (Yamane et al., 2006), JMJD2A/JHDM3A (Tsukada et al., 2006; Whetstine et al., 2006), JMJD2B (Fodor et al., 2006), JMJD2C/GASC1 (Cloos et al., 2006), and JMJD2D (Shin and Janknecht, 2006).”

“The dogma, that H3K9 methylation and HP1 recruitment are always repressive, has recently been challenged by the finding that H3K9me3 and the g isoform of HP1 are enriched in the coding region of active genes (Vakoc et al., 2005).”

“Their selectivity for mono-, di-, or trimehylated lysines allows for a larger functional control of lysine methylation (Shi and Whetstine, 2007).”

“Enzymes have been identified for acetylation (Sterner and Berger, 2000), methylation (Zhang and Reinberg, 2006), phosphorylation (Nowak and Corces, 2004), ubiquitination (Shilatifard, 2006), sumoylation (Nathan et al., 2006), ADP-ribosylation (Hassa et al., 2006), deimination (Cuthbert et al., 2004; Wang et al., 2004b…”

“A role for this modification has been demonstrated in transcriptional elongation by the histone chaperone FACT (Pavri et al., 2006).”

“The PHD-finger protein ING2 tethers the repressive mSin3a-HDAC1 histone deacetylases complex to highly active, proliferation-specific genes after the exposure of cells to DNA-damaging agents (Pena et al., 2006; Shi et al., 2006).”

“…the initiation site that are hypoacetylated at certain lysines and are enriched in the H2A variant Hzt1 (Liu et al., 2005; Zhang et al., 2005; Raisner et al., 2005; Millar et al., 2006; Millar and Grunstein, 2006); the initiation site itself is devoid of nucleosomes; lysine trimethylation is…”

“The fission yeast class III deacetylase Sir2 has some selectivity for H4K16ac, and recently the human Sir family member SirT2 has been demonstrated to have a similar preference (Vaquero et al., 2006).”

“In the process of analyzing the stoichiometric partners of the ING family of proteins, HB01 was found in a complex with ING4 (a tumor suppressor) and ING5 (Doyon et al., 2006).”

“Two phosphorylation sites on this histone have a role in doublestrand break repair via nonhomologous end joining: H2AS129 mediated by Mec1 (Downs et al., 2000) and H4S1 mediated by Caesin kinase II (Cheung et al.”

“Enzymes have been identified for acetylation (Sterner and Berger, 2000), methylation (Zhang and Reinberg, 2006), phosphorylation (Nowak and Corces, 2004), ubiquitination (Shilatifard, 2006), sumoylation (Nathan et al.”

“In budding yeast phosphorylation of H2AX has been shown to recruit the INO80 complex, which possesses ATP-dependant remodeling activity (Van Attikum et al., 2004).”

“In contrast, H2BK120 ubiquitylation is mediated by human RNF20/RNF40 and UbcH6 and in budding yeast by Rad6/Bre1 and is activatory for transcription (Zhu et al., 2005).”

“(B) The Crb2 protein of fission yeast is recruited to DNA-repair foci during a DNA-repair response.”

“…two nucleosomes flanking the initiation site that are hypoacetylated at certain lysines and are enriched in the H2A variant Hzt1 (Liu et al., 2005; Zhang et al., 2005; Raisner et al., 2005; Millar et al., 2006; Millar and Grunstein, 2006); the initiation site itself is devoid of nucleosomes;…”

“One role for H3K36me is the suppression of inappropriate initiation from cryptic start sites within the coding region (Carrozza et al., 2005; Cuthbert et al., 2004; Joshi and Struhl, 2005; Keogh et al., 2005).”

“…to chromatin, but in these instances the enzymatic activity resides within the methyl-binding protein: JMJD2A is a histone lysine demethylase that binds via a tudor domain and CHD1 is an ATPase that binds via a chromodomain (Huang et al., 2006; Pray-Grant et al., 2005; Sims et al., 2005).”

“Ubiquitylation of H2AK119 is mediated by the Bmi/Ring1A protein found in the human polycomb complex and is associated with transcriptional repression (Wang et al., 2006).”

“Most of the information we have has come from global analyses in budding yeast (Liu et al., 2005; Pokholok et al., 2005).”

“Converting citrulline to arginine has not been described, although citrulline is cyclic on the pS2 promoter, so reversal may be possible (Bannister and Kouzarides, 2005).”

“The JMJD2A lysine demethylase has been demonstrated to bind H3K20me (Huang et al., 2006; Kim et al., 2006) via a tudor domain.”

“Like lysine methylation, arginine methylation can be either activatory or repressive for Cell 128, 693–705, February 23, 2007 ª2007 Elsevier Inc. 699 transcription, and the enzymes (protein arginine methyltransferases, PRMT’s) are recruited to promoters by transcription factors (Lee et al., 2005b).”

“…to chromatin, but in these instances the enzymatic activity resides within the methyl-binding protein: JMJD2A is a histone lysine demethylase that binds via a tudor domain and CHD1 is an ATPase that binds via a chromodomain (Huang et al., 2006; Pray-Grant et al., 2005; Sims et al., 2005).”

“A yeast protein SPT10 may be mediating acetylation of H3K56 at the promoters of histone genes to regulate gene expression (Xu et al., 2005), whereas the Rtt109 acetyltransferase mediates this modification more globally (Han et al., 2007; Driscoll et al., 2007; Schneider et al., 2006).”

“…to chromatin, but in these instances the enzymatic activity resides within the methyl-binding protein: JMJD2A is a histone lysine demethylase that binds via a tudor domain and CHD1 is an ATPase that binds via a chromodomain (Huang et al., 2006; Pray-Grant et al., 2005; Sims et al., 2005).”

“A yeast protein SPT10 may be mediating acetylation of H3K56 at the promoters of histone genes to regulate gene expression (Xu et al., 2005), whereas the Rtt109 acetyltransferase mediates this modification more globally (Han et al., 2007; Driscoll et al., 2007; Schneider et al., 2006).”

“Thirdly, the catalytic activity of an enzyme could be compromised by modification of its substrate recognition site; for example, isomerization of H3P38 affects methylation of H3K36 by Set2 (Nelson et al., 2006).”

“Small RNAs may emanate from many loci in the genome and once transmitted to the next generation, these RNAs may deliver chromatin-modifying complexes to specific genes or to specific locations, thus generating the pattern of chromatin that we observe (Verdel et al., 2004; Buhler et al., 2006).”

“A yeast protein SPT10 may be mediating acetylation of H3K56 at the promoters of histone genes to regulate gene expression (Xu et al., 2005), whereas the Rtt109 acetyltransferase mediates this modification more globally (Han et al., 2007; Driscoll et al., 2007; Schneider et al., 2006).”

“H3K9 can also be demethylated by JHDM2A (Yamane et al., 2006), JMJD2A/JHDM3A (Tsukada et al., 2006; Whetstine et al., 2006), JMJD2B (Fodor et al., 2006), JMJD2C/GASC1 (Cloos et al., 2006), and JMJD2D (Shin and Janknecht, 2006).”

“The study of such pathways is less detailed, but examples include H3K4me disrupting the binding of the NuRD complex and H3T3ph preventing the binding of the INHAT complex.”

“In contrast, H2BK120 ubiquitylation is mediated by human RNF20/RNF40 and UbcH6 and in budding yeast by Rad6/Bre1 and is activatory for transcription (Zhu et al., 2005).”

“Thirdly, the catalytic activity of an enzyme could be compromised by modification of its substrate recognition site; for example, isomerization of H3P38 affects methylation of H3K36 by Set2 (Nelson et al., 2006).”

“…are found may specify a preference for nucleosomal verses free histones (Lee et al., 2005a); proteins that associate with the enzyme may affect its selection of residue to modify (Metzger et al., 2005) or the degree of methylation (mono-, di-, or tri-) at a specific site (Steward et al., 2006).”

“Certain common features have come to light regarding the composition and enrichment of modifications on actively transcribed genes: acetylation is enriched at specific sites in the promoter and 50 end of the coding regions; within the promoter there are two nucleosomes flanking the initiation site that are hypoacetyla…”

“However, in the presence of DNA damage the deacetylases for H3K56, Hst3, and Hst4 (two paralogs of Sir2) are downregulated and the modification persists (Celic et al., 2006; Maas et al., 2006).”

“Concomitant with this phosphorylation is the appearance on chromatin of a phosphor-binding protein 14-3-3 (Macdonald et al., 2005).”

“…that are hypoacetylated at certain lysines and are enriched in the H2A variant Hzt1 (Liu et al., 2005; Zhang et al., 2005; Raisner et al., 2005; Millar et al., 2006; Millar and Grunstein, 2006); the initiation site itself is devoid of nucleosomes; lysine trimethylation is enriched in the…”

“In Drosophila, the HB01 homolog, Chameau, is found to increase the firing of replication origins (Aggarwal and Calvi, 2004).”

“provides an adaptor function, augmenting the recognition of H3K4me (Ruthenburg et al., 2006).”

“However, structural analysis of this interaction does not support a purely methyl-recognitionbased interaction but suggests that this protein binds most avidly to the residues preceding H3K4 and in particular to H3R2 (Couture et al., 2006).”

“Monoubiquitylation of H2A is also implicated in UV-induced repair (Bergink et al., 2006).”

“Phosphorylation of H4S1 regulates sporulation (Krishnamoorthy et al., 2006), and phosphorylation of H2BS10 regulates peroxide-induced apoptosis (Ahn et al., 2005).”

“Recently, a global ChIP on CHIP analysis of many kinases in budding yeast has shown that they are present on the chromatin of specific genes (Pokholok et al., 2006).”

“However, in the presence of DNA damage the deacetylases for H3K56, Hst3, and Hst4 (two paralogs of Sir2) are downregulated and the modification persists (Celic et al., 2006; Maas et al., 2006).”

“A yeast protein SPT10 may be mediating acetylation of H3K56 at the promoters of histone genes to regulate gene expression (Xu et al., 2005), whereas the Rtt109 acetyltransferase mediates this modification more globally (Han et al., 2007; Driscoll et al., 2007; Schneider et al., 2006).”

“New methodology that uses a top-down proteomics approach (identify protein first and digest subsequently) gives promise that we may, in the future, look at the intact modification pattern of different histones in a given nucleosome ( Macek et al., 2006 ).”

“One of the earliest recognized responses to DNA damage is the phosphorylation of the histone variant g-H2AX in mammalian cells (Fillingham et al., 2006).”

“In a separate study HB01 is shown to augment the assembly of the pre-replicative complex and the recruitment of MCMs to chromatin (Iizuka et al., 2006).”

“The Ubp10 deubiquitylase functions in transcriptional silencing at heterochromatic sites in budding yeast (Emre et al., 2005; Gardner et al., 2005).”

“The Ubp10 deubiquitylase functions in transcriptional silencing at heterochromatic sites in budding yeast (Emre et al., 2005; Gardner et al., 2005).”

“A role for H3S10 phosphorylation has been demonstrated for the activation of NFKB-regulated genes and also ‘‘immediate early’’ genes such as c-fos and c-jun.”

“Two phosphorylation sites on this histone have a role in doublestrand break repair via nonhomologous end joining: H2AS129 mediated by Mec1 (Downs et al., 2000) and H4S1 mediated by Caesin kinase II (Cheung et al., 2005).”

“H3K9 can also be demethylated by JHDM2A (Yamane et al., 2006), JMJD2A/JHDM3A (Tsukada et al., 2006; Whetstine et al., 2006), JMJD2B (Fodor et al., 2006), JMJD2C/GASC1 (Cloos et al., 2006), and JMJD2D (Shin and Janknecht, 2006).”

“This phosphor-binding domain may recognize the DNA-damage-induced phosphorylation site and then stabilize itself on chromatin via the recognition of H4K20me ( Du et al., 2006 ).”

“Phosphorylation of H4S1 regulates sporulation (Krishnamoorthy et al., 2006), and phosphorylation of H2BS10 regulates peroxide-induced apoptosis (Ahn et al., 2005).”

“This enzyme is recruited to sites of DNA repair and acetylates H4K12 (Qin and Parthun, 2006).”

“In vitro analysis of the PADI4 enzyme suggests that the reversal of monomethyl arginine to citrulline is not carried out by the recombinant enzyme when methylated peptides are used as substrates, suggesting that a cofactor may be necessary in vivo (Hidaka et al., 2005).”

“The dogma, that H3K9 methylation and HP1 recruitment are always repressive, has recently been challenged by the finding that H3K9me3 and the g isoform of HP1 are enriched in the coding region of active genes (Vakoc et al., 2005).”