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2016 ; 7
(6
): 532-539
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Insight into the machinery that oils chromatin dynamics
#MMPMID27893319
Wright RH
; Fernandez-Fuentes N
; Oliva B
; Beato M
Nucleus
2016[Nov]; 7
(6
): 532-539
PMID27893319
show ga
The packaging of genetic information in form of chromatin within the nucleus
provides cells with the ability to store and protect massive amounts of
information within a compact space. Storing information within chromatin allows
selective access to specific DNA sequences by regulating the various levels of
chromatin structure from nucleosomes, to chromatin fibers, loops and topological
associating domains (TADs) using mechanisms that are being progressively
unravelled. However, a relatively unexplored aspect is the energetic cost of
changing the chromatin configuration to gain access to DNA information. Among the
enzymes responsible for regulating chromatin access are the ATP-dependent
chromatin remodellers that act on nucleosomes and use the energy of ATP
hydrolysis to make chromatin DNA more accessible. It is assumed that the ATP used
by these enzymes is provided by the mitochondria or by cytoplasmic glycolysis. We
hypothesize that though this may be the case for cells in steady state, when gene
expression has to be globally reprogramed in response to externals signals or
stress conditions, the cell directs energy production to the cell nucleus, where
rapid chromatin reorganization is needed for cell survival. We discovered that in
response to hormones a nuclear ATP synthesis mechanism is activated that
utilizing ADP-ribose and pyrophosphate as substrates. (1) This extra view aims to
put this process within its historical context, to describe the enzymatic steps
in detail, to propose a possible structure of the ATP synthesising enzyme, and to
shed light on how this may link to other reactions within the cell providing a
perspective for future lines of investigation.