Histone Modification And Chromatin Structure And Gene

Expression In Plants

Submitted to:

Dr.Shafiq ur Rehman

Submitted by:

Fiza Siddique (5069)

Department:

BS (Hons) Zoology

Semester:

3nd Evening

UNIVERSITY OF OKARA
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Histone Modification And Chromatin Structure And Gene Expression In
Plants

ABSTRACT

Plants respond and adapt to drought, cold and high-salinity stress in order to survive.
Molecular and genomic studies have revealed that many stress-inducible genes with various
functions and signaling factors, such as transcription factors, protein kinases and protein
phosphatases, are involved in the stress responses. Recent studies have revealed the
coordination of the gene expression and chromatin regulation in response to the environmental
stresses. Several histone modifications are dramatically altered on the stress-responsive gene
regions under drought stress conditions. Several chromatin-related proteins such as histone
modification enzymes, linker histone HI and components of chromatin remodeling complex
influence the gene regulation in the stress responses. This review briefly describes chromatin
regulation in response to drought, cold and high-salinity stress.

INTRODUCTION

Environmental abiotic stresses, such as drought, cold and high salinity, affect plant
growth. These stresses induce various biochemical and physiological responses in plants.
Several thousand genes that respond to these stresses at the transcriptional level have been
identified. Among them, a number of regulatory proteins, such as transcription factors, and
functional proteins, such as osmoprotectant synthesis-related proteins, have been shown to
function in the plant stress response and tolerance.

Recent studies have indicated that regulation of stress responsive genes often depends
on chromatin remodeling, that is, the process inducing changes in chromatin structure. Changes
in chromatin structure are related with modification of the N-terminal tails of histones. Several
chromatin-related proteins, such as histone modification enzymes, are involved in this process.

In this review, we highlight recent data on chromatin regulation in plant responses to drought,
cold and high salinity stress.

Histone modification changes under abiotic stress conditions

Post-translational modification of histone N-tails affects eukaryotic gene activity. In

Arabidopsis, 28 histone modification sites have been identified by mass spectrometry and

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chromatin immunoprecipitation (ChIP) analyses. Recently, several reports on the changes in
histone modification under abiotic stresses in plants have been published.

ChIP assay showed that histone modifications on the H3 N-tail are altered with gene
activation on the coding regions of four Arabidopsis drought stress-responsive genes such as
responsive to dehydration (RD)29A, RD29B and RD20, and an AP2 domain-containing
transcription factor (At2g20880) in response to drought stress. Enrichments of trimethylation
of histone H3 Lys4 (H3K4me3) and acetylation of histone H3 Lys9 (H3K9ac), often used as a
positive marker of histone modifications associated with gene activity, correlate with gene
activation in response to drought stress in all four drought-inducible genes. Enrichment of
acetylation of histone H3 Lys23 (H3K23ac) and acetylation of histone H3 Lys27 (H3K27 ac)
occurs in response to drought stress on the coding regions of RD29B, RD20 and At2g20880,
but not on the coding region of RD29A, indicating that enrichment of H3K23ac and H3K27ac
occurs in response to drought stress in a gene-specific manner. Interestingly, establishment of
H3K4me3 enrichment occurs after full activation of RD29A and At2g20880 transcription in
response to drought stress.

Kwon et al. showed that trimethylation of histone H3 Lys27 (H3K27me3), a negative

histone modification marker for transcription, is decreased in two Arabidopsis cold-responsive
genes, cold-regulated (COR)15A and ATGOLS3 (Taji et al. 2002 encoding galactinol synthase
(GOLS), during exposure to cold temperature by ChIP assay. The decrease of H3K27me3 is
maintained for up to 3 d after a return to normal growth temperature, while the mRNA
accumulation of the COR15A and ATGOLS3 was repressed at 1 d after the removal of the cold
stress. These results suggest that enrichment of H3K27me3 can be inher¬ited to some degree
through cell divisions. However, the previous cold-induced decrease of H3K27me3 level of
the two genes did not enhance the transcriptional induction after re-exposure to cold stress.

Sokol et al applied Western blot analysis to study nucleosomal response in cultured

cells of Arabidopsis T87 and tobacco BY-2 cell lines, and showed that phosphorylation of
histone H3 SerlO, phospho acetylation of histone H3 at SerlO and Lys14 and acetylation of
histone H4 were increased by high-salinity, cold and abscisic acid (ABA) treatments. The
observed nucleosomal response was consistent with the up-regulation of the stress-inducible
genes.

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 In rice, modification levels of acetylation of histone H3, dimethylation of histone H3
Lys4 (H3K4me2) and trimethylation of histone H3 Lys4 (H3K4me3) were altered on
submergence-inducible genes, alcohol dehydrogenase 1

(ADH1) and pyruvate decarboxylase 1 (PDC1) during the process from submergence
to re-aeration. The submergence treatments resulted in the decrease of H3K4me2leveis and
increase of H3K4me3leveis on the 5'¬and 3'-coding regions of ADHl and PDCl genes. Histone
H3 acetylation was gradually increased on the ADHl and PDCl genes with submergence
treatment. These histone modification levels recovered to the initial levels after re-aeration
treatment.

Histone modification enzymes

Changes in chromatin structures are related with modification of the N-terminal tails of
the histones. Histone modification enzymes, such as histone acetyltransferase (HAT), histone
de acetylase (HDAC), histone methyltransferase (HMT) and histone demethylase (HDM),
function in the modification of the N-terminal tails of the histones, and are an essential factor
for chromatin remodeling.

Several HATs are responsible for transcriptional activation through the acetylation of
lysine residues on the histone N-tails. In Arabidopsis, there are 12 HAT proteins including
three members of general control non-derepressible (GCNS)¬related N-terminal
acetyltransferase (GNAT) family, two members of MOZ, YbF2, Sas2, Tip60-like (MYST)
family,Their information is also available at the Chromatin Database.

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 AtGCNS, a homolog of yeast GCNS, is one of the most studied HAT proteins in
Arabidopsis. AtGCNS is involved in transcriptional responses to environmental changes, such
as cold-regulated gene expression and light-regulated gene expression, and in developmental
processes of flowers. The AtGCNS protein interacts in vitro with the transcriptional adaptor
proteins Ada2a and Ada2b. The non-acclimated ada2b mutants showed more freezing tolerance
phenotype compared with the non-acclimated wild-type plants.

Figure 1. A possible chromatin regulation mechanism involving changes in histone modification and

nucleosome occupancy in response to drought stress. Chromatin regulation-related components are shown in
red. HAT, histone

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 acetyl transferase; HDAC, histone deacetylase; HMG, high-mobility group (HMG)
proteins; HMT, histone methyltransferase; Hl-3,linker histone Hl-3; RNAPII, RNA
polymerase II; TF, transcription factor. See text for details

The yeast two-hybrid assay showed that AtGCNS interacts with a protein phosphatase
2C protein (AtPP2C-6-6) (Servet et al. 2008). The AtGCNS protein is dephosphorylated by
AtPP2C-6-6 in vitro. Expression of several stress inducible genes, responsive to ABA
(RAB)18, RD29A, RD29B and COR15A, were reduced under the high-salinity stress in
atpp2c-6-6 mutants, while in the atgcn5 mutants, the expression of the stress-inducible genes
was not affected by high-salinity stress, but the expression of RAB18 and RD29B was
increased in unstressed condition. Western blot analysis showed that acetylation levels of
histone H3K14 and H3K27 were not changed greatly in atpp2c-6-6 mutants and that these
histone acetylation levels were reduced in atgcn5 mutants. Although these results indicate that
AtPP2C-6-6 is required for the induction of several stress inducible genes, it is not clear
whether the function of AtPP2C-6-6 in stress responses is achieved through its interaction with
AtGCNS.

The mutants of the Arabidopsis homologs of the four subunits of yeast Elongator HAT
complex, ELP2, ELP6, ELP42/ELOl and ELPlIABA-overly sensitive 1 (AB01)/ EL02 showed
the phenotypes of oxida¬tive stress tolerance, ABA hypersensitivity and increased
accumulation of anthocyanin. Among them, the mutations in the ELPlIABOllEL02 and ELP2
genes caused stomatal closing and ABA supersensitive. The four mutants of the Elongator
subunits had increased transcript levels of a catalase (CAT3) gene under normal conditions and
of ZAT10 gene, a C2H2-zinc finger-type transcription factor whose gain and loss-of-function
mutations enhance the tolerance to salinity, heat and osmotic stress. These results suggest that
Elongator plays a role in regulating ABA responses and oxidative stress tolerance.

HDACs are generally responsible for repression of gene activity through the de
acetylation of lysine residue on the histone N-tails. In Arabidopsis, there are 18 HDACs,
including 12 members of RPD3/HDAl superfamily, four members of plant-specific HD2
family and two members of SIR2 family.

Gene expression:
Gene expression of the HD2C, a plant-specific HD2-type HDAC in Arabidopsis, was
repressed by ABA treatment. 35S:AtHD2C-GFP seedlings were insensitive to ABA. In wild-

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type plants, seed germination and root elongation were inhibited at 0.1 .uM ABA. On the other
hand, they were not inhibited in 35S:AtHD2C-GFP transgenic plants under the same
conditions. In addition, at 100 mn NaCl, germination and root elongation of 35S:AtHD2C-GFP
plants were not inhibited compared with wild-type plants . Expression of several ABA-
responsive genes, such as RD29B and RAB18, was up-regulated in 35S:AtHD2C-GFP plants,
indicating that AtHD2C can modulate ABA and stress responses.

The Arabidopsis high expression of osmotically responsive genes (hos) 15 mutant was
hypersensitive to freezing stress. HOS15 encodes a protein similar to human transducin-{3-
like protein (TBe), a component of a repressor protein complex involved in histone
deacetylation. The acetylation level of histone H4 was higher in the hos15 mutants than in
wild-type plants, suggesting that HOS15 is involved in de acetylation of histone H4.

In rice, there are 18 HDACs including 14 members of RPD3/HDAl superfamily, two

members of HD2 family and two members of SIR2 family. Semi-quantitative RT-PCR analysis
revealed that the expression of several rice HDAC genes respond differently to abiotic stresses
and to hormones such as ABA. ABA repressed the expression of HDT701 and SRT701 genes,
members of HD2 family and SRT702 gene, a member of SIR2 family. Abiotic stresses, such
as mannitol and cold stress, repressed the expression of SRT701 gene. In barley, semi-
quantitative RT-PCR analysis revealed that the expression of HvHDAC2-2 gene, a member of
HD2 family, was repressed at 6 h after ABA treatment. Recent Arabidopsis tiling array analysis
also showed that the expression of several chromatin regulation-related genes including histone
modification enzymes is influenced by drought, high-salinity stress and ABA.

Recently, the transgenic Arabidopsis co-suppression lines (msil-cs) of MSll gene,

encoding a subunit of Polycomb group protein complexes and chromatin assembly factor 1,
showed increased drought stress tolerance phenotype. In the msil-cs lines, the expression of
many ABA-responsive genes were upregulated. The ChIP assay demonstrated that the drought
inducible RD20 gene is a direct target of MSIl.

Changes in nucleosome occupancy under abiotic stress conditions

Generally, nucleosome occupancy is negatively correlated with transcriptional

activation. When the transcription is activated in a genomic region, nucleosome density is
decreased and the chromatin structure is relaxed.

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 The ChIP assay using anti-histone H3 C-terminal antibody indicated that two types of
regulation of nucleosome occupancy function in the drought stress response. The first type is
that nucleosome density on the promoter regions is low compared with that of coding regions,
and there is no notable nucleosome loss on the coding regions under drought stress. This type
is observed in RD29A and RD29B genes. Note that the nucleosome density of RD29A and
RD29B promoter regions containing key drought stress-responsive cis-elements, dehydration-
responsive element (DRE)/C-repeat or ABA-responsive element (ABRE) motifs is low. This
might contribute to the rapid binding of the transcription factors, such as DRE¬binding protein
(DREB)/C-repeat-binding factor (CBF)and ABRE-binding protein (AREB)I ABRE-binding
factor (ABF) in response to drought stress. The second type is that nucleosome density is
gradually decreased in response to drought stress. This type is observed in RD20 and
At2g20880 genes.

Kwon et al. showed that the histone occupancy is decreased on the promoter regions of
COR15A and ATGO LS3 genes in response to cold stress by the ChIP assay. The histone H3
occupancy did not change greatly after the return to normal growth temperature except for the
promoter region of ATGOLS3. The histone H3 density in the ATGO LS3 promoter region
increased in 1 d after the return and decreased in 3 d, suggesting that the changes in histone H3
occupancy might be coupled to the ATGOLS3 transcription.

Chromatin-associated proteins

Chromatin-associated proteins, such as linker histones and high-mobility group (HMG)

proteins, function in gene and chromatin regulation by changing the higher-order structure of
chromatin such as nucleosome packing and chromatin assembly.

Linker histone H1

Linker histone HI is an important molecule to regulate the chromatin structure and gene
activity. Linker histone HI binds to the linker DNA between nucleosome cores, thus facilitating
the compaction of chromatin. In Arabidopsis genome, there are three linker histone HI
homologs. Among them, the expression of HISl-3 gene is induced by drought stress and ABA
treatments. The expression of the HISl-3 gene was repressed in abil mutants subjected to the
drought stress treatments. Analysis of transgenic plants containing the promoter:f3-
glucuronidase (GUS) fusion showed that HISl-3 gene was highly expressed in root meristem
and elongation zone of the drought-stressed young plants. Fujita et al. showed that the

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expression of the HISl-3 gene is up-regulated in plants over-expressing an activated form of
AREBI transcription factor encoding ABRE¬binding protein. These results indicate that the
HISl-3 gene is a target one regulated by AREBI. Transgenic plants overexpressing the active
form of AREBI showed ABA hypersensitivity and enhanced drought tolerance.

A linker histone variant gene, HISl-S, has been identified as a drought- and ABA-
induced one in tomato.Analysis of transgenic plants containing Hl-S:GUS fusion showed that
the Hl-S protein accumulates in the nuclei and that it is associated with chromatin of wilted
tomato leaves. Hl-S antisense transgenic plants had a faster decrease in relative water content
(RWC) of leaves compared with wild-type plants. Physiological analyses showed that stomatal
conductance and transpiration rate were higher in the Hl-S antisense transgenic plants than in
wild-type plants, indicating that Hl-S functions in regulating and modulating an important
mechanism involved in the regulation of stomatal function.

HMG proteins

The chromosomal HMG proteins are abundant and highly mobile chromatin-associated
proteins that influence chromatin structure, and typically contain a central HMG-box DNA-
binding domain.In plants, proteins that belong to the HMGA and HMGB families containing
AT-hook DNA-binding motifs and HMG-box domains, respectively, have been identified.

Over-expression of Arabidopsis HMGBI protein decreased the seed germination rate

under high-salinity stress conditions.The seed germination in the presence of methyl methane
sulphonate (MMS), a monofunctional DNA alkylating agent, was affected in both HMGBl-
deficient lines and the overexpresses. Microarray analysis of the HMGBl-deficient lines
showed that the stress-inducible genes, such as HISl-3 and a LEA protein-encoding one, are
down-regulated. The most significantly down-regulated gene ontology (GO) category was
stress-responsive genes. No significant differences between HMGBl-deficient lines and wild-
type in the overall chromatin structures were observed by the immunofluorescence experiments
using antibodies against several histone H3 modifications, suggesting that HMGBI does not
affect changes in the histone H3 modification levels.

The expression of Arabidopsis HMGB2, HMGB3 and HMGB4 genes was up-regulated
by cold stress, whereas the expression of the HMGB2 and HMGB3 genes was markedly down-
regulated by drought or high-salinity stress.Under high-salinity stress, the HMGB2- over-
expressing Arabidopsis plants modulated the expression of several germination-responsive

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genes, and displayed retarded germination and subsequent growth compared with wild-type
plants .

The Arabidopsis HMGBl, HMGB2/3 and HMGB4 proteins are phosphorylated by

casein kinase 2a (CK2a) (Stemmer et al. 2003), and the phosphorylation of the Drosophila
HMGl proteins by CK2 is important for their proper folding, stability and DNA-binding
specificity.The phosphorylation of the HMGB proteins by CK2 might have a role in stress
responses.

ATP-dependent chromatin remodeling factors The switch (SWI)/sucrose non-

fermenting (SNF) complex is a multisubunit DNA-dependent ATPase that contributes to the
regulation of gene transcription by alteration of chromatin structure.The positions and/or
structure of nucleosomes are altered by the SWII SNF complex that can use the energy of ATP
hydrolysis.

Over-expression of AtCHRI2, a SNF2/Brahma (BRM)¬type chromatin remodeling

factor in Arabidopsis, resulted in growth arrest of primary buds, as well as in reduced growth
of the primary stems in response to drought and heat stress. On the other hand, the atchr12
knockout mutant shows less growth arrest than the wild type under stress. These results indicate
that AtCHR12 plays a role in mediating the temporary growth arrest in response to the drought
and heat stress.

A two-hybrid analysis revealed that SWI3B, an Arabidopsis homolog of the SWI3 core
subunit of SWIISNF complex, is a prevalent partner of hypersensitive to ABAI (HABl), a
protein phosphatase 2C playing a key role as a negative regulator of ABA signaling. The swi3b
mutants showed a reduced sensitivity to ABA-mediated inhibition of seed germination and
growth, and reduced expression of the ABA-responsive genes, such as RD29B and RAB18.
ChIP assay showed that the presence of HABI in the vicinity of the ABA-responsive RD29B
and RAB18 promoters is abolished by ABA. These results suggest that HABI modulates ABA
response through the regulation of the SWIISNF complex containing SWI3B.

The expression of PsSNF5 gene encoding a pea homolog of the SNF5 protein in the
SWIISNF complex was up-regulated by ABA and drought stress treatments. The yeast two-
hybrid assay showed that PsSNF5 interacts with Arabidopsis AtSWI3A and AtSWI3B,
suggesting that chromatin remodeling induced by PsSNF5- containing complex might
contribute to the response to ABA and drought stress.

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DNA methylation changes under stress conditions

DNA cytosine methylation, both asymmetric (mCpHpH, H is adenine, cytosine or

thymine) methylation and symmetric (mCpG and mCpHpG) methylation, is associated with
repression of gene transcription. De novo DNA methyl¬transferases domains rearranged
methylase 1 (DRMl) and DRM2 catalyse new cytosine methylation, while the maintenance of
symmetric CG and CHG methylation is mediated by the DNMTI-like enzyme METI and the
plant specific enzyme chromomethylase 3 (CMT3), respectively.

Several reports showed that stresses can induce changes in hypomethylation of DNA.
In tobacco, DNA methylation is reduced in the coding region of a glycerophosphodiesterase-
like gene (NtGPDL) after aluminum, salt and cold stress treatments, and its reduction was
correlated with the NtGPDL expression. In maize roots, cold stress-up-regulated expression of
ZmMIl gene that contains part of the coding region of a putative protein and a retrotransposon-
like sequence was correlated with the reduction of DNA methylation of the nucleosome core
regions. In Arabidopsis, DNA methylation at the 180 bp centromeric repeat and other loci is
reduced by infection with the bacterial pathogen Pseudomonas syringae .

CONCLUSIONS AND FUTURE PERSPECTIVES

Stress-inducible changes in modification on the histone N-tail and nucleosome

occupancy are involved in the regulation of the stress-responsive gene expression. Dynamic
alteration of modifications in the histone N-tail has been shown to correlate with gene
activation in response to the stress. ChIP-sequencing analysis using next-generation
sequencing technology, such as Solexa, Inc. (http://www.solexa.com/) and Applied
Biosystems,and ChIP-chip analysis using the tiling array will enable the genome-wide
identification of changes in histone modification and nucleosome occupancy under abiotic
stress.

Several chromatin regulation-related factors, such as histone modification enzymes,

linker histone HI, HMG proteins and ATP-dependent chromatin remodeling factors have been
shown to function in plant abiotic stress responses. Identifying the key chromatin regulation-
related factors including histone modification enzymes is indispensable for understanding the
transcriptional regulatory network of the abiotic stress responses.

Epigenetic modifications such as histone modifications and DNA methylation might

confer within-generational and transgenerational stress memory to the plant. It is unknown

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whether epigenetic changes induced by abiotic stress might have an adaptive advantage for
stress tolerance. It is important to identify the heritable epigenetic modifications induced by
abiotic stress to understand the phenomenon of stress memory.

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