Tax abolishes histone H1 repression of p300 acetyltransferase activity at the human T-cell leukemia virus type 1 promoter.

Abstract

Upon infection of human T-cell leukemia virus type 1 (HTLV-1), the provirus is integrated into the host cell genome and subsequently packaged into chromatin that contains histone H1. Consequently, transcriptional activation of the virus requires overcoming the environment of chromatin and H1. To efficiently activate transcription, HTLV-1 requires the virally encoded protein Tax and cellular transcription factor CREB. Together Tax and CREB interact with three cis-acting promoter elements called viral cyclic-AMP response elements (vCREs). Binding of Tax and CREB to the vCREs promotes association of p300/CBP into the complex and leads to transcriptional activation. Therefore, to fully understand the mechanism of Tax transactivation, it is necessary to examine transcriptional activation from chromatin assembled with H1. Using a DNA template harboring the complete HTLV-1 promoter sequence and a highly defined recombinant assembly system, we demonstrate proper incorporation of histone H1 into chromatin. Addition of H1 to the chromatin template reduces HTLV-1 transcriptional activation through a novel mechanism. Specifically, H1 does not inhibit CREB or Tax binding to the vCREs or p300 recruitment to the promoter. Rather, H1 directly targets p300 acetyltransferase activity. Interestingly, in determining the mechanism of H1 repression, we have discovered a previously undefined function of Tax, overcoming the repressive effects of H1-chromatin. Tax specifically abrogates the H1 repression of p300 enzymatic activity in a manner independent of p300 recruitment and without displacement of H1 from the promoter.

• Authors: Kasey L Konesky, Jennifer K Nyborg, Paul J Laybourn
• Journal: Journal of virology (J Virol) Vol. 80 Issue 21 Pg. 10542-53 (Nov 2006) ISSN: 0022-538X [Print] United States
• PMID: 16943293 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cell Cycle Proteins
• Chromatin
• Cyclic AMP Response Element-Binding Protein
• DNA, Viral
• Drosophila Proteins
• Gene Products, tax
• Histones
• Transcription Factors
• Histone Acetyltransferases
• p300-CBP Transcription Factors
• p300-CBP-associated factor

Topics

• Animals
• Base Sequence
• Cell Cycle Proteins (antagonists & inhibitors, metabolism)
• Cell Line
• Chromatin (genetics, metabolism)
• Cyclic AMP Response Element-Binding Protein (metabolism)
• DNA, Viral (genetics, metabolism)
• Drosophila
• Drosophila Proteins (metabolism)
• Gene Products, tax (genetics, metabolism)
• Genes, pX
• Histone Acetyltransferases (antagonists & inhibitors, metabolism)
• Histones (metabolism)
• Human T-lymphotropic virus 1 (genetics, physiology)
• Humans
• Models, Biological
• Promoter Regions, Genetic
• Protein Binding
• Transcription Factors (antagonists & inhibitors, metabolism)
• Transcriptional Activation
• Virus Assembly
• p300-CBP Transcription Factors