Component of the ACF complex, an ATP-dependent chromatin remodeling complex, that regulates spacing of nucleosomes using ATP to generate evenly spaced nucleosomes along the chromatin. The ATPase activity of the complex is regulated by the length of flanking DNA. Also involved in facilitating the DNA replication process. BAZ1A is the accessory, non-catalytic subunit of the complex which can enhance and direct the process provided by the ATPase subunit, SMARCA5, probably through targeting pericentromeric heterochromatin in late S phase. Moves end-positioned nucleosomes to a predominantly central position. May have a role in nuclear receptor-mediated transcription repression.
Arrays of regularly spaced nucleosomes directly correlate with closed chromatin structures at silenced loci. The ATP-dependent chromatin-assembly factor (ACF) generates such arrays in vitro and is required for transcriptional silencing in vivo. A key unresolved question is how ACF 'measures' equal spacing between nucleosomes. We show that ACF senses flanking DNA length and transduces length information in an ATP-dependent manner to regulate the rate of nucleosome movement. Using fluorescence resonance energy transfer to follow nucleosome movement, we find that ACF can rapidly sample DNA on either side of a nucleosome and moves the longer flanking DNA across the nucleosome faster than the shorter flanking DNA. This generates a dynamic equilibrium in which nucleosomes having equal DNA on either side accumulate. Our results indicate that ACF generates the characteristic 50- to 60-base-pair internucleosomal spacing in silent chromatin by kinetically discriminating against shorter linker DNAs.
Hormones and vitamins play integral roles in modulating transcriptional activity of members of the nuclear hormone receptor (NR) superfamily. The nuclear receptor corepressor protein (N-CoR) is essential for the transcriptional repression by unliganded NRs. In an attempt to isolate novel components of the hormone signaling pathway, we used a yeast two-hybrid screen and identified human ATP-utilizing chromatin assembly and remodeling factor 1 (hAcf1) as an N-CoR interacting protein. A previously unrecognized function of hAcf1 in the repression of euchromatic genes in mammalian cells was found: hAcf1 plays key roles in the hormone responsiveness and in the transcriptional repression of specific class II NR-regulated genes. First, hormone treatment causes a significant release of hAcf1 from its target gene promoters. Second, hAcf1 is crucial for stabilizing the endogenous vitamin D receptor-N-CoR repression complex and N-CoR itself, in the vitamin D3-regulated IGF binding protein 3 and receptor activator of nuclear factor-kappaB ligand gene promoters, respectively. Third, RNA interference-mediated reduction of hAcf1 or vitamin D3 treatment differentially affects the histone modification profile and the histone occupancy in these genes. Together, these results establish that hAcf1 has a critical role in the transcriptional repression of specific NR-regulated genes and indicate that hAcf1 release and histone H3 and H4 eviction are novel mechanisms in hormone-induced gene activation.
The histone fold is a structural motif with which two related proteins interact and is found in complexes involved in wrapping DNA, the nucleosome, and transcriptional regulation, as in NC2. We reveal a novel function for histone-fold proteins: facilitation of nucleosome remodeling. ACF1-ISWI complex (ATP-dependent chromatin assembly and remodeling factor [ACF]) associates with histone-fold proteins (CHRAC-15 and CHRAC-17 in the human chromatin accessibility complex [CHRAC]) whose functional relevance has been unclear. We show that these histone-fold proteins facilitate ATP-dependent nucleosome sliding by ACF. Direct interaction of the CHRAC-15/17 complex with the ACF1 subunit is essential for this process. CHRAC-17 interacts with another histone-fold protein, p12, in DNA polymerase epsilon, but CHRAC-15 is essential for interaction with ACF and enhancement of nucleosome sliding. Surprisingly, CHRAC-15/17, p12/CHRAC-17, and NC2 complexes facilitate ACF-mediated chromatin assembly by a mechanism different from nucleosome sliding enhancement, suggesting a general activity of H2A/H2B type histone-fold complexes in chromatin assembly.
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.
Component of the histone-fold protein complex CHRAC complex which faciliates nucleosome sliding by the ACF complex and enhances ACF-mediated chromatin assembly. The C-terminal regions of both CHRAC1 and POLE1 are required for these functions.
Hormones and vitamins play integral roles in modulating transcriptional activity of members of the nuclear hormone receptor (NR) superfamily. The nuclear receptor corepressor protein (N-CoR) is essential for the transcriptional repression by unliganded NRs. In an attempt to isolate novel components of the hormone signaling pathway, we used a yeast two-hybrid screen and identified human ATP-utilizing chromatin assembly and remodeling factor 1 (hAcf1) as an N-CoR interacting protein. A previously unrecognized function of hAcf1 in the repression of euchromatic genes in mammalian cells was found: hAcf1 plays key roles in the hormone responsiveness and in the transcriptional repression of specific class II NR-regulated genes. First, hormone treatment causes a significant release of hAcf1 from its target gene promoters. Second, hAcf1 is crucial for stabilizing the endogenous vitamin D receptor-N-CoR repression complex and N-CoR itself, in the vitamin D3-regulated IGF binding protein 3 and receptor activator of nuclear factor-kappaB ligand gene promoters, respectively. Third, RNA interference-mediated reduction of hAcf1 or vitamin D3 treatment differentially affects the histone modification profile and the histone occupancy in these genes. Together, these results establish that hAcf1 has a critical role in the transcriptional repression of specific NR-regulated genes and indicate that hAcf1 release and histone H3 and H4 eviction are novel mechanisms in hormone-induced gene activation.
Arrays of regularly spaced nucleosomes directly correlate with closed chromatin structures at silenced loci. The ATP-dependent chromatin-assembly factor (ACF) generates such arrays in vitro and is required for transcriptional silencing in vivo. A key unresolved question is how ACF 'measures' equal spacing between nucleosomes. We show that ACF senses flanking DNA length and transduces length information in an ATP-dependent manner to regulate the rate of nucleosome movement. Using fluorescence resonance energy transfer to follow nucleosome movement, we find that ACF can rapidly sample DNA on either side of a nucleosome and moves the longer flanking DNA across the nucleosome faster than the shorter flanking DNA. This generates a dynamic equilibrium in which nucleosomes having equal DNA on either side accumulate. Our results indicate that ACF generates the characteristic 50- to 60-base-pair internucleosomal spacing in silent chromatin by kinetically discriminating against shorter linker DNAs.
The histone fold is a structural motif with which two related proteins interact and is found in complexes involved in wrapping DNA, the nucleosome, and transcriptional regulation, as in NC2. We reveal a novel function for histone-fold proteins: facilitation of nucleosome remodeling. ACF1-ISWI complex (ATP-dependent chromatin assembly and remodeling factor [ACF]) associates with histone-fold proteins (CHRAC-15 and CHRAC-17 in the human chromatin accessibility complex [CHRAC]) whose functional relevance has been unclear. We show that these histone-fold proteins facilitate ATP-dependent nucleosome sliding by ACF. Direct interaction of the CHRAC-15/17 complex with the ACF1 subunit is essential for this process. CHRAC-17 interacts with another histone-fold protein, p12, in DNA polymerase epsilon, but CHRAC-15 is essential for interaction with ACF and enhancement of nucleosome sliding. Surprisingly, CHRAC-15/17, p12/CHRAC-17, and NC2 complexes facilitate ACF-mediated chromatin assembly by a mechanism different from nucleosome sliding enhancement, suggesting a general activity of H2A/H2B type histone-fold complexes in chromatin assembly.
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.
The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.
Interacting selectively and non-covalently with any protein or protein complex (a complex of two or more proteins that may include other nonprotein molecules).
Evidence
1:
Inferred from Physical InteractionUniProtKB
Hormones and vitamins play integral roles in modulating transcriptional activity of members of the nuclear hormone receptor (NR) superfamily. The nuclear receptor corepressor protein (N-CoR) is essential for the transcriptional repression by unliganded NRs. In an attempt to isolate novel components of the hormone signaling pathway, we used a yeast two-hybrid screen and identified human ATP-utilizing chromatin assembly and remodeling factor 1 (hAcf1) as an N-CoR interacting protein. A previously unrecognized function of hAcf1 in the repression of euchromatic genes in mammalian cells was found: hAcf1 plays key roles in the hormone responsiveness and in the transcriptional repression of specific class II NR-regulated genes. First, hormone treatment causes a significant release of hAcf1 from its target gene promoters. Second, hAcf1 is crucial for stabilizing the endogenous vitamin D receptor-N-CoR repression complex and N-CoR itself, in the vitamin D3-regulated IGF binding protein 3 and receptor activator of nuclear factor-kappaB ligand gene promoters, respectively. Third, RNA interference-mediated reduction of hAcf1 or vitamin D3 treatment differentially affects the histone modification profile and the histone occupancy in these genes. Together, these results establish that hAcf1 has a critical role in the transcriptional repression of specific NR-regulated genes and indicate that hAcf1 release and histone H3 and H4 eviction are novel mechanisms in hormone-induced gene activation.
Dynamic structural changes to eukaryotic chromatin occurring throughout the cell division cycle. These changes range from the local changes necessary for transcriptional regulation to global changes necessary for chromosome segregation.
The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.
The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.
The bromodomain is a structural motif characteristic of proteins involved in chromatin-dependent regulation of transcription. Bromodomain proteins have been identified as integral components of chromatin remodeling complexes and frequently possess histone acetyltransferase activity. Their encoding genes have been identified at translocation breakpoints, and at least one, CBP, is a tumor suppressor gene. We have identified a series of novel bromodomain genes by EST database and cDNA library screening. Comparison of sequences for four clones indicated that they represent genes belonging to a novel bromodomain family. Full-length sequences for these genes, which are widely expressed, predict encoded proteins of between 1527 and 1972 amino acids. In addition to a carboxy-terminal bromodomain, an adjacent PHD finger, and a WACZ motif, at least four other conserved novel motifs are present in each protein. The genes contain regions conserved with Drosophila Acf1 and Caenorhabditis elegans ZK783.4. The novel genes, termed BAZ1A, BAZ1B, BAZ2A, and BAZ2B, localize to chromosomes 14q12-q13, 7q11-q21, 12q24.3-qter, and 2q23-q24, respectively. Conservation of multiple domains throughout these genes with Acf1 indicates that they are likely to be components of chromatin remodeling complexes.
Protein involved in the transfer of genetic information from DNA to messenger RNA (mRNA) by DNA-directed RNA polymerase. In the case of some RNA viruses, protein involved in the transfer of genetic information from RNA to messenger RNA (mRNA) by RNA-directed RNA polymerase.
A reference proteome is a set of protein sequences derived from a complete proteome which constitutes a defined standard for a particular user community. Reference proteomes are manually defined according to a number of criteria. They cover the proteomes of well- studied model organisms and other proteomes of interest for biomedical and biotechnological research. Reference proteomes have been selected to provide broad coverage of the tree of life, and constitute a representative cross-section of the taxonomic diversity to be found within UniProtKB.
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