Laboratory of Genome Structure and Function
Graduate School of Science
Professor

Chikashi OBUSEobuse

Associate Professor Koji NAGAO

nagao

Assistant Professor

s.isobeShinya ISOBE

URL: https://www.bio.sci.osaka-u.ac.jp/bio̲web/lab̲page/obuse/
The ability of cells to store, retrieve, andtranslate genetic information is essential for thedevelopment and sustaining of living organisms.
The genetic information of mammalian cells ispreserved in the nucleus, in which DNA together
with proteins and RNA form a complex calledchromatin. Different types of cells in our bodyare originated from one cell, fertilized egg. Thus,
such different types of cells still possess the same
genetic information, but their cellular identities
are determined by each cell-type-specific gene
expression. This cell-type-specific gene
expression pattern is controlled by epigenetic
information including DNA methylation, histone
post-translational modifications, and chromatin
structure. This epigenetic information or
epigenomes can be changed during
differentiation or by environmental factors, but
are also maintained and inherited by the next
generation if cellular identity is fixed. We areinterested in genetic and epigenetic mechanisms
to inherit genetic information and utilize it
properly. In addition, we want to understandhow cell-type-specific epigenome can beswitched or maintained through cell division at
the molecular level. We employ omics
approaches using mass spectrometry and nextgeneration sequencer, as well as molecularbiological and genetical, biochemical, and cellbiological approaches, to elucidate these issues.

How epigenome is converted into higherorder chromatin structures
Chemical modifications of histones and DNA
regulate gene expression by converting them intohigher-order chromatin structures. For example, inheterochromatin, condensed chromatin structure
prevents accession of transcription factors to DNA toinhibit transcription. We are trying to elucidate
mechanisms of how epigenomic marks are converted
into chromatin structures. For example, the inactive
X chromosome in females has a condensed
chromatin structure and represses almost all genes
on it. We clarified that proteins we identified
specifically bind an epigenomic mark to form
condensed chromatin structure in cooperation with
noncoding RNA, XIST.
Diseases caused by a catastrophe in themechanisms of the epigenome
A catastrophe of the mechanisms in the epigenome
can lead to a variety of diseases. For example, thedysfunction of proteins involved in the condensationof inactive X chromosomes we discovered, has beenshown to cause certain types of muscular
dystrophies. Our understanding of the epigenome
mechanism is expected to lead to a better
understanding of the molecular basis of the causes
and pathophysiology of diseases, which subsequently
will contribute to the diagnosis and treatment ofthese diseases.
Omics-based Research on the Epigenome

How epigenome is inherited to andoverwritten by the next generation.
In these years, the functional expression of genes
in response to cell differentiation and stimuli hascome to be thought to be regulated by marks on
chromatin such as chemical modifications ofhistones and DNA, the so-called epigenome. Thesemarks can be inherited or overwritten by the next
generation without changing the genome DNAsequence. A single cell, the fertilized egg,
proliferates and is into a terminally differentiatedcell through various cell fates. During this process,the genetic information in the genome DNA isaccurately preserved over the cell division, while theepigenome, which directs gene expression pattern
for differentiation, is continually being overwritten.
On the other hand, to maintain the terminallydifferentiated state, the epigenome must be
accurately inherited to the next generation over thecell division. We are elucidating these mechanisms
through analysis of uncharacterized chromatinproteins that we have originally discovered in humancells by a proteomic approach.

In our laboratory, we use comprehensive
analytical methods that utilize genome sequence
information. For example, using mass spectrometer,
we can identify the name of even a very small
amount of a protein. Using this technology, we are
discovering uncharacterized proteins that are
involved in the epigenome mechanism successively.
In addition, the next-generation sequencer is a
powerful device; we can find out where on thechromatin the protein we have identified is locatedand what function it performs.

Fig. 1 DNA, accompanied by proteins such as histones andRNA, forms chromatin and is stored in the nucleus.

Figure 2 The nucleus of a female cell. Specific chemical
modifications of the histones (green, red) are enriched in
the condensed inactive X chromosome.

Figure 3 Mass spectrometer; for identification of trace
amounts of proteins.

This mechanism is still full ofDepartment of Biological Sciences
Graduate School of Science, Osaka University
1-1, Machikaneyama-cho, Toyonaka, Osaka
560-0043, Japan

mysteries. Let's try to solve theTEL: +81-6-6850-5812

The regulation of the epigenome
is involved in various life events.

mystery together!

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