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Molecular and Cellular Biology, January 2000, p. 523-529, Vol. 20, No. 2
Protein Section, Laboratory of Molecular
Carcinogenesis, Division of Basic Sciences, National Cancer
Institute,1 and Laboratory of Molecular
Growth Regulation, National Institute of Child Health and Human
Development,2 National Institutes of
Health, Bethesda, Maryland 20892
Received 26 August 1999/Returned for modification 1 October
1999/Accepted 22 October 1999
Although a link between histone acetylation and transcription has
been established, it is not clear how acetylases function in the
nucleus of the cell and how they access their targets in a chromatin
fiber containing H1 and folded into a highly condensed structure. Here
we show that the histone acetyltransferase (HAT) p300/CBP-associated
factor (PCAF), either alone or in a nuclear complex, can readily
acetylate oligonucleosomal substrates. The linker histones, H1 and H5,
specifically inhibit the acetylation of mono- and oligonucleosomes and
not that of free histones or histone-DNA mixtures. We demonstrate that
the inhibition is due mainly to steric hindrance of H3 by the tails of
linker histones and not to condensation of the chromatin fiber.
Cellular PCAF, which is complexed with accessory proteins in a
multiprotein complex, can overcome the linker histone repression. We
suggest that linker histones hinder access of PCAF, and perhaps other
HATs, to their target acetylation sites and that perturbation of the
linker histone organization in chromatin is a prerequisite for
efficient acetylation of the histone tails in nucleosomes.
0270-7306/0/$04.00+0
Histone H1 Is a Specific Repressor of Core Histone
Acetylation in Chromatin
*
Corresponding author. Mailing address: Protein Section,
LMC, NCI, NIH, Bldg. 37, Room 3D20, Bethesda, MD 20892. Phone: (301) 496-2885. Fax: (301) 496-8419. E-mail:
herr{at}helix.nih.gov.
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