Are linker histones (histone H1)
dispensable for survival?
Juan Ausio
Â
Summary
In the multicelled filamentous ascomycete
Ascolobus
immersus
, the single copy gene for histone H1 can be
silenced by methylation in the process known as
methylation-induced premeiotically (MIP). The results of
a recent paper using this unique system
(1)
have shown
that histone H1 silencing results in an enhanced DNA
accessibility to nucleases and an increase in the overall
extent of DNA methylation. Interestingly, while none of
these effects appear to decrease the immediate viability
of this fungus, silencing of histone H1 results in a
significant decrease in its overall life span. These results
suggest that while linker histones may be dispensable for
the relatively short life span of an individual cell, they are
most likely indispensable for survival of higher eukaryote
organisms. BioEssays 22:873±877, 2000.
ß 2000 John Wiley & Sons, Inc.
Introduction
The proteins of the histone H1 family are found associated
with the linker DNA regions connecting adjacent nucleo-
somes in eukaryotic chromatin and hence they are also
referred to as ``linker histones''. Binding of linker histones
induces condensation of the chromatin filament into a 30 nm
fiber and numerous in vitro studies have shown that these
proteins play a very important role in the modulation of folding
of the chromatin fiber.
(2)
In contrast to core histones (histones H2A, H2B, H3 and
H4), linker histones exhibit a significantly higher extent of
microheterogeneity
(3,4)
and show much less evolutionary
conservation.
(5)
The evolutionary variability of these proteins
may be taken as an indication of their relatively less critical
contribution to chromatin function.
The role of histone H1 and its dispensability for cell sur-
vival has been the subject of several analyses in recent
years.
(1,6±8)
While it was convincingly shown in these studies
that histone H1 is dispensable for the short term viability of the
organism, the effects of histone H1 complete depletion on
long term survival were not clearly elucidated.
A valuable system to understand the
relationship between histone H1, DNA
methylation, and gene silencing
Like other filamentous fungi,
(8,9)
the genome of Ascolobus
immersus contains a single copy gene for histone H1.
(1)
The
deduced amino acid sequence indicates that this histone H1
has the tripartite structural organization that is characteristic
of the metazoan H1 histones
(1,9)
in which a gobular central
domain is flanked by less structured N and C-terminal
domains.
In the course of sexual reproduction, the filamentous
fungus Ascolobus has the ability to methylate and silence
multiple copy genes through a process known as methylation
induced premeiotically (MIP).
(10)
It is thus possible to use
genetic transformation to introduce a duplicate form of a
given gene, or set of genes, and then obtain strains that are
identical to the native type but which contain two copies of the
same gene or set of genes, one of which has been silenced by
methylation. Furthermore , the duplication transformants can
then be crossed to target methylation to the native histone H1
gene and produce strains that entirely lack expression for
histone H1. The system therefore offers a very valuable tool
to study the effects of silencing of histone H1 by DNA methy-
lation, including any consequences on long term survival of
the organism.
Histone H1 depletion affects chromatin
structure and the long-term life span
of the organism
An earlier insight into the dispensability of linker histones
came from the study of the effects of histone H1 depletion in
the ciliated protozoan Tetrahymena thermophila.
(6)
This
single celled organism has a dimorphic nuclei: A polyploid
macronucleus and a diploid micronucleus (involved in sexual
reproduction, i.e. conjugation). Each one contains a single
copy gene of histone H1. In the case of the micronucleus
histone H1 consists of four proteins that are the product of
proteolytic processing from a 70 kDa precursor.
(6)
The use of
gene disruption allowed the creation of Tetrahymena strains
that lacked either the macronuclear histone H1, the micro-
nuclear histone H1 proteins or both. All these strains were
fully viable, exhibiting very similar growth to that of the wild-
type strains. In all instances, however, histone H1 depletion
resulted in significant chromatin decondensation. The effects
BioEssays 22:873±877, ß 2000 John Wiley & Sons, Inc. BioEssays 22.10 873
Department of Biochemistry and Microbiology, University of Victoria,
Petch Building 220, Victoria, British Columbia, Canada V8W 3P6.
E-mail: jausio@uvic.ca
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