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attributable to their recruitment of a histone acetyltransferase, but other
times, the factors themselves contain HAT activity. For example, p300,
a binding partner of CREB, has been demonstrated to contain histone
associated with CREB-mediated gene transcription is the protein CBP
(CREB-binding protein). This protein contains a HAT domain and is
predominantly associated with H3K4 acetylation. This is generally associ-
be important for H3K27 acetylation, a modification which takes place
ates these rhythmic modifications in part by being rhythmically recruited
of CBP in rhythmic gene transcription appears to be complex, however,
as CBP also interacts with the period 2 protein (PER2), thereby parti-
cipating in the negative limb of the negative transcriptional loop of the
H3K4 modifier, inducing acetylation and subsequent gene activation at
relevant gene sites.
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1.3. Histone deacetylases under circadian control
There are a number of histone deacetylase (HDAC) enzymes that have been
demonstrated as circadian in expression or activity. The circadian expression
or activity of these proteins is equally important in circadian gene expression
as proteins with HAT activity as HDACs remove acetyl groups from his-
tones and nonhistone proteins, ultimately affecting activity that is dependent
on acetylation state. Among the HDACs associated with circadian control,
the sirtuin family members may be among the most famous HDACs. The
sirtuin family of proteins has been recognized for its peripheral and central
roles in both circadian rhythmicity and metabolism. The sirtuin family is
composed of seven family members, which display unique subcellular local-
ization. Specifically, some sirtuins are mitochondrial (SIRT3, SIRT4, and
SIRT5) and others are principally cytoplasmic (SIRT2) nuclear (SIRT1,
SIRT6, and SIRT7) or expressed in several compartments within the cell.
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Sir2 (silent information regulator 2, the homolog of the mammalian SIRT1)
is a nicotinamide adenine dinucleotide (NAD
รพ
)-dependent HDAC, and
mammalian ortholog of Sir2, SIRT1, has become a well-recognized
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