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Molecular and Cellular Biology, January 2000, p. 523-529, Vol. 20, No. 2
0270-7306/0/$04.00+0

Histone H1 Is a Specific Repressor of Core Histone Acetylation in Chromatin

Julio E. Herrera,1,* Katherine L. West,1 R. Louis Schiltz,2 Yoshihiro Nakatani,2 and Michael Bustin1

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.


* 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.


Molecular and Cellular Biology, January 2000, p. 523-529, Vol. 20, No. 2
0270-7306/0/$04.00+0



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