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Computational Molecular Biology 2014, Vol. 4, No. 10, 1-17
http://cmb.biopublisher.ca
1
Research Article Open Access
Genomic and functional characterization of histone H3 lysine 4 methylation
co-localized marks
Jie Lv
1
, Hongbo Liu
1
, Hui Liu
1
, Qiong Wu
1
, Yan Zhang
2
1. School of Life Science and Technology, Harbin Institute of Technology, Harbin, 150001, China
2. College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China
Corresponding author email
QW)
(YZ)
Computational Molecular Biology, 2014, Vol.4, No.10 doi: 10.5376/cmb.2014.04.0010
Received: 07 Sep., 2014
Accepted: 25 Oct., 2014
Published: 14 Nov., 2014
© 2014
Lv et al., This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use,
distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:
Lv et al., 2014,
Genomic and functional characterization of histone H3 lysine 4 methylation co-localized marks
, Computational Molecular Biology,
Vol.4, No.10, 1-17
(doi
Abstract
Histone modifications play important roles in dynamic transcription regulation. In mammals, methylation of lysine 4 in
histone H3 (H3K4) is associated with open chromatin environment. From functional genomic perspective, the combinations of
methylation co-localized marks in lysine residue 4 of histone H3 (H3K4me) are little studied. The genomic patterns of specific
H3K4me co-localized peaks are highly conserved. Additionally, the proteins encoded by genes with co-localization peaks in
promoter regions have more partners in protein-protein interaction network. We also found the unbalanced base composition, that is,
AT nucleotide is preferred in genomic regions with co-localization H3K4me modifications. Gene Ontology enrichment analysis
revealed that genes with specific co-localization modifications in promoter regions are function-specific. We also found the PolII
level for different combinations are correlated with the differential methyl accumulation of H3K4. Me1me2me3, the triplet for
H3K4me, is associated with tissue specificity. This study helps understanding the genomic features of H3K4me co-localization and
the role of H3K4me co-localization in function genomic regulation.
Keywords
Histone modifications; Co-localization; Genomic composition; CpG islands; H3K4me
Introduction
In eukaryote, the chromatin is packed by consecutive
octamers comprised by basic histone types H2A, H2B,
H3 and H4, around which DNA sequences of 147bp
are wrapped. The histones can be altered by different
post-translational chemical groups, leading to different
biological effects. Acetyl, methyl, phosphoryl and
ubiquityl are the most common post-translational
chemical group types. Straightforwardly, a common
question may be raised by researchers: do different
histone modifications bring out distinct biological
outcomes? The histone code hypothesis may answer
the question
.
According to the hypothesis, specific histone
modification combination can act coordinately to form
a barcode which is read by other outer proteins to
bring about various biological effects. Though the
“histone code” hypothesis is debated, arising
evidences are emerging to support the hypothesis
. Histone methylation has been
associated with activating and repressive functions. In
mouse embryonic stem cells, developmental genes are
marked both by the activating H3K4me3 and the
repressive H3K27me3 (‘bivalent’)
.
Besides the patterns of different histone modifications
at different residues of histones are complex, patterns
for different number of methyl groups that modify the
same residues are also complex. The ε-amino group of
lysines can be mono-, di-, or trimethylated with
potentially distinct effects on chromatin structure
. In yeast, a H3K4
methyltransferase (SET1) is identified
and the kinetics of the separation of SET1 from
the elongating RNA polymerase is associated with the
differential methylation of H3K4. In
Arabidopsis
thaliana
, distinct H3K4 methyltransferase complexes
contribute to differential accumulation of H3K4 at
specific residues. For example, the dysfunction of
H3K4 methyltransferase ATX1 can lead to decreased