Mechanical Regulation of the Proangiogenic Factor CCN1/CYR61 Gene Requires the Combined Activities of MRTF-A and CREB-binding Protein Histone Acetyltransferase

ABSTRACT Nuclear factor-κB (NF-κB) plays a role in the transcriptional regulation of genes involved in inflammation and cell survival. In this report we demonstrate that NF-κB recruits a coactivator complex that has striking similarities to that recruited by nuclear receptors. Inactivation of either cyclic AMP response element binding protein (CREB)-binding protein (CBP), members of the p160 family of coactivators, or the CBP-associated factor (p/CAF) by nuclear antibody microinjection prevents NF-κB-dependent transactivation. Like nuclear receptor-dependent gene expression, NF-κB-dependent gene expression requires specific LXXLL motifs in one of the p160 family members, and enhancement of NF-κB activity requires the histone acetyltransferase (HAT) activity of p/CAF but not that of CBP. This coactivator complex is differentially recruited by members of the Rel family. The p50 homodimer fails to recruit coactivators, although the p50-p65 heterodimeric form of the transcription factor assembles the integrator complex. These findings provide new mechanistic insights into how this family of dimeric transcription factors has a differential effect on gene expression.

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Interplay Between BALL and CREB Binding Protein Maintains H3K27 Acetylation on Active Genes in Drosophila

Frontiers in Cell and Developmental Biology ◽

10.3389/fcell.2021.740866 ◽

2021 ◽

Vol 9 ◽

Author(s):

Ammad Shaukat ◽

Muhammad Haider Farooq Khan ◽

Hina Ahmad ◽

Zain Umer ◽

Muhammad Tariq

Keyword(s):

Histone Acetyltransferase ◽

Binding Protein ◽

Gene Activation ◽

Creb Binding Protein ◽

Drastic Reduction ◽

Trithorax Group ◽

Genome Wide ◽

Histone Kinase ◽

Trithorax Group Proteins ◽

Active Genes

CREB binding protein (CBP) is a multifunctional transcriptional co-activator that interacts with a variety of transcription factors and acts as a histone acetyltransferase. In Drosophila, CBP mediated acetylation of histone H3 lysine 27 (H3K27ac) is a known hallmark of gene activation regulated by trithorax group proteins (trxG). Recently, we have shown that a histone kinase Ballchen (BALL) substantially co-localizes with H3K27ac at trxG target loci and is required to maintain gene activation in Drosophila. Here, we report a previously unknown interaction between BALL and CBP, which positively regulates H3K27ac. Analysis of genome-wide binding profile of BALL and CBP reveals major overlap and their co-localization at actively transcribed genes. We show that BALL biochemically interacts with CBP and depletion of BALL results in drastic reduction in H3K27ac. Together, these results demonstrate a previously unknown synergy between BALL and CBP and reveals a potentially new pathway required to maintain gene activation during development.

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The Transcriptional Co-activators CREB-binding Protein (CBP) and p300 Play a Critical Role in Cardiac Hypertrophy That Is Dependent on Their Histone Acetyltransferase Activity

Journal of Biological Chemistry ◽

10.1074/jbc.m211762200 ◽

2002 ◽

Vol 278 (9) ◽

pp. 6838-6847 ◽

Cited By ~ 130

Author(s):

Rosalind J. Gusterson ◽

Elen Jazrawi ◽

Ian M. Adcock ◽

David S. Latchman

Keyword(s):

Cardiac Hypertrophy ◽

Histone Acetyltransferase ◽

Binding Protein ◽

Critical Role ◽

Creb Binding Protein ◽

Acetyltransferase Activity ◽

Histone Acetyltransferase Activity

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Transcriptional Regulation of the MDR1 Gene by Histone Acetyltransferase and Deacetylase Is Mediated by NF-Y

Molecular and Cellular Biology ◽

10.1128/mcb.18.7.4377 ◽

1998 ◽

Vol 18 (7) ◽

pp. 4377-4384 ◽

Cited By ~ 214

Author(s):

Shengkan Jin ◽

Kathleen W. Scotto

Keyword(s):

Transcriptional Activation ◽

Histone Acetyltransferase ◽

Binding Protein ◽

Trichostatin A ◽

Present Report ◽

Dominant Negative ◽

Creb Binding Protein ◽

Wild Type ◽

Ccaat Box

ABSTRACT Recent studies have shown that the histone-modifying enzymes histone acetyltransferase (HAT) and histone deacetylase (HDAC) are involved in transcriptional activation and repression, respectively. However, little is known about the endogenous genes that are regulated by these enzymes or how specificity is achieved. In the present report, we demonstrate that HAT and HDAC activities modulate transcription of the P-glycoprotein-encoding gene, MDR1. Incubation of human colon carcinoma SW620 cells in 100-ng/ml trichostatin A (TSA), a specific HDAC inhibitor, increased the steady-state level ofMDR1 mRNA 20-fold. Furthermore, TSA treatment of cells transfected with a wild-type MDR1 promoter/luciferase construct resulted in a 10- to 15-fold induction of promoter activity. Deletion and point mutation analysis determined that an inverted CCAAT box was essential for this activation. Consistent with this observation, overexpression of p300/CREB binding protein-associated factor (P/CAF), a transcriptional coactivator with intrinsic HAT activity, activated the wild-type MDR1 promoter but not a promoter containing a mutation in the CCAAT box; deletion of the P/CAF HAT domain abolished activation. Gel shift and supershift analyses identified NF-Y as the CCAAT-box binding protein in these cells, and cotransfection of a dominant negative NF-Y expression vector decreased the activation of the MDR1promoter by TSA. Moreover, NF-YA and P/CAF were shown to interact in vitro. This is the first report of a natural promoter that is modulated by HAT and HDAC activities in which the transcription factor mediating this regulation has been identified.

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Acetylation of Histones and Transcription-Related Factors

Microbiology and Molecular Biology Reviews ◽

10.1128/mmbr.64.2.435-459.2000 ◽

2000 ◽

Vol 64 (2) ◽

pp. 435-459 ◽

Cited By ~ 1075

Author(s):

David E. Sterner ◽

Shelley L. Berger

Keyword(s):

Histone Acetyltransferase ◽

Binding Protein ◽

Rna Polymerase Iii ◽

High Mobility ◽

General Factor ◽

Creb Binding Protein ◽

Related Factors ◽

Nuclear Receptor Coactivators ◽

Chromatin Proteins ◽

Related Proteins

SUMMARY The state of chromatin (the packaging of DNA in eukaryotes) has long been recognized to have major effects on levels of gene expression, and numerous chromatin-altering strategies—including ATP-dependent remodeling and histone modification—are employed in the cell to bring about transcriptional regulation. Of these, histone acetylation is one of the best characterized, as recent years have seen the identification and further study of many histone acetyltransferase (HAT) proteins and their associated complexes. Interestingly, most of these proteins were previously shown to have coactivator or other transcription-related functions. Confirmed and putative HAT proteins have been identified from various organisms from yeast to humans, and they include Gcn5-related N-acetyltransferase (GNAT) superfamily members Gcn5, PCAF, Elp3, Hpa2, and Hat1: MYST proteins Sas2, Sas3, Esa1, MOF, Tip60, MOZ, MORF, and HBO1; global coactivators p300 and CREB-binding protein; nuclear receptor coactivators SRC-1, ACTR, and TIF2; TATA-binding protein-associated factor TAFII250 and its homologs; and subunits of RNA polymerase III general factor TFIIIC. The acetylation and transcriptional functions of these HATs and the native complexes containing them (such as yeast SAGA, NuA4, and possibly analogous human complexes) are discussed. In addition, some of these HATs are also known to modify certain nonhistone transcription-related proteins, including high-mobility-group chromatin proteins, activators such as p53, coactivators, and general factors. Thus, we also detail these known factor acetyltransferase (FAT) substrates and the demonstrated or potential roles of their acetylation in transcriptional processes.

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