Solution structures of the N-terminal domain of histone H4

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.

Download Full-text

Determinants of Histone H4 N-terminal Domain Function during Nucleosomal Array Oligomerization

Journal of Biological Chemistry ◽

10.1074/jbc.m109.011288 ◽

2009 ◽

Vol 284 (25) ◽

pp. 16716-16722 ◽

Cited By ~ 23

Author(s):

Steven J. McBryant ◽

Joshua Klonoski ◽

Troy C. Sorensen ◽

Sarah S. Norskog ◽

Sere Williams ◽

...

Keyword(s):

Histone H4 ◽

Terminal Domain ◽

Nucleosomal Array

Download Full-text

Solution Structures of the C-Terminal Domain of Cardiac Troponin C Free and Bound to the N-Terminal Domain of Cardiac Troponin I

Biochemistry ◽

10.1021/bi995088b ◽

1999 ◽

Vol 38 (43) ◽

pp. 14432-14432

Author(s):

Geneviève M. C. Gasmi-Seabrook ◽

Jack W. Howarth ◽

Natosha Finley ◽

Ekram Abusamhadneh ◽

Vadim Gaponenko ◽

...

Keyword(s):

Cardiac Troponin ◽

Troponin I ◽

Troponin C ◽

Cardiac Troponin I ◽

Solution Structures ◽

Cardiac Troponin C ◽

Terminal Domain

Download Full-text

TFIIH-Associated Cdk7 Kinase Functions in Phosphorylation of C-Terminal Domain Ser7 Residues, Promoter-Proximal Pausing, and Termination by RNA Polymerase II

Molecular and Cellular Biology ◽

10.1128/mcb.00637-09 ◽

2009 ◽

Vol 29 (20) ◽

pp. 5455-5464 ◽

Cited By ~ 184

Author(s):

Kira Glover-Cutter ◽

Stéphane Larochelle ◽

Benjamin Erickson ◽

Chao Zhang ◽

Kevan Shokat ◽

...

Keyword(s):

Rna Polymerase ◽

Rna Polymerase Ii ◽

Elongation Factor ◽

Histone H4 ◽

Pol Ii ◽

Terminal Domain ◽

Histone H4 Acetylation ◽

Flanking Regions

ABSTRACT The function of human TFIIH-associated Cdk7 in RNA polymerase II (Pol II) transcription and C-terminal domain (CTD) phosphorylation was investigated in analogue-sensitive Cdk7 as/as mutant cells where the kinase can be inhibited without disrupting TFIIH. We show that both Cdk7 and Cdk9/PTEFb contribute to phosphorylation of Pol II CTD Ser5 residues on transcribed genes. Cdk7 is also a major kinase of CTD Ser7 on Pol II at the c-fos and U snRNA genes. Furthermore, TFIIH and recombinant Cdk7-CycH-Mat1 as well as recombinant Cdk9-CycT1 phosphorylated CTD Ser7 and Ser5 residues in vitro. Inhibition of Cdk7 in vivo suppressed the amount of Pol II accumulated at 5′ ends on several genes including c-myc, p21, and glyceraldehyde-3-phosphate dehydrogenase genes, indicating reduced promoter-proximal pausing or polymerase “leaking” into the gene. Consistent with a 5′ pausing defect, Cdk7 inhibition reduced recruitment of the negative elongation factor NELF at start sites. A role of Cdk7 in regulating elongation is further suggested by enhanced histone H4 acetylation and diminished histone H4 trimethylation on lysine 36—two marks of elongation—within genes when the kinase was inhibited. Consistent with a new role for TFIIH at 3′ ends, it was detected within genes and 3′-flanking regions, and Cdk7 inhibition delayed pausing and transcription termination.

Download Full-text

Acetylation of the Entamoeba histone H4 N-terminal domain is influenced by short-chain fatty acids that enter trophozoites in a pH-dependent manner

International Journal for Parasitology ◽

10.1016/j.ijpara.2007.06.007 ◽

2008 ◽

Vol 38 (1) ◽

pp. 57-64 ◽

Cited By ~ 6

Author(s):

Jennifer Byers ◽

Daniel Eichinger

Keyword(s):

Fatty Acids ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Dependent Manner ◽

Histone H4 ◽

Terminal Domain ◽

Ph Dependent ◽

Chain Fatty Acids

Download Full-text

Hit and run versus long-term activation of PARP-1 by its different domains fine-tunes nuclear processes

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1901183116 ◽

2019 ◽

Vol 116 (20) ◽

pp. 9941-9946 ◽

Cited By ~ 16

Author(s):

Colin Thomas ◽

Yingbiao Ji ◽

Chao Wu ◽

Haily Datz ◽

Cody Boyle ◽

...

Keyword(s):

Specific Binding ◽

Histone H4 ◽

Short Term ◽

Terminal Domain ◽

Specific Binding Sites ◽

Hit And Run ◽

Nuclear Processes ◽

Parp 1 ◽

Continuous Accumulation

Poly(ADP-ribose) polymerase 1 (PARP-1) is a multidomain multifunctional nuclear enzyme involved in the regulation of the chromatin structure and transcription. PARP-1 consists of three functional domains: the N-terminal DNA-binding domain (DBD) containing three zinc fingers, the automodification domain (A), and the C-terminal domain, which includes the protein interacting WGR domain (W) and the catalytic (Cat) subdomain responsible for the poly(ADP ribosyl)ating reaction. The mechanisms coordinating the functions of these domains and determining the positioning of PARP-1 in chromatin remain unknown. Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as well as consisting of only one of those domains, we demonstrate that different functions of PARP-1 are coordinated by interactions among these domains and their targets. Interaction between the DBD and damaged DNA leads to a short-term binding and activation of PARP-1. This “hit and run” activation of PARP-1 initiates the DNA repair pathway at a specific point. The long-term chromatin loosening required to sustain transcription takes place when the C-terminal domain of PARP-1 binds to chromatin by interacting with histone H4 in the nucleosome. This long-term activation of PARP-1 results in a continuous accumulation of pADPr, which maintains chromatin in the loosened state around a certain locus so that the transcription machinery has continuous access to DNA. Cooperation between the DBD and C-terminal domain occurs in response to heat shock (HS), allowing PARP-1 to scan chromatin for specific binding sites.

Download Full-text

The highly conserved N-terminal domains of histones H3 and H4 are required for normal cell cycle progression.

Molecular and Cellular Biology ◽

10.1128/mcb.11.8.4111 ◽

1991 ◽

Vol 11 (8) ◽

pp. 4111-4120 ◽

Cited By ~ 61

Author(s):

B A Morgan ◽

B A Mittman ◽

M M Smith

Keyword(s):

Cell Cycle ◽

Normal Cell ◽

Cell Cycle Progression ◽

Histone H3 ◽

Temperature Sensitive ◽

Histone H4 ◽

Cycle Progression ◽

Terminal Domain ◽

Normal Cell Cycle ◽

Terminal Domains

The N-terminal domains of the histones H3 and H4 are highly conserved throughout evolution. Mutant alleles deleted for these N-terminal domains were constructed in vitro and examined for function in vivo in Saccharomyces cerevisiae. Cells containing a single deletion allele of either histone H3 or histone H4 were viable. Deletion of the N-terminal domain of histone H4 caused cells to become sterile and temperature sensitive for growth. The normal cell cycle progression of these cells was also altered, as revealed by a major delay in progression through the G2 + M periods. Deletion of the N-terminal domain of histone H3 had only minor effects on mating and the temperature-sensitive growth of mutant cells. However, like the H4 mutant, the H3 mutants had a significant delay in completing the G2 + M periods of the division cycle. Double mutants containing N-terminal domain deletions of both histone H3 and histone H4 were inviable. The phenotypes of cells subject to this synthetic lethality suggest that the N-terminal domains are required for functions essential throughout the cell division cycle and provide genetic evidence that histones are randomly distributed during chromosome replication.

Download Full-text

Crystal and solution structures reveal oligomerization of individual capsid homology domains of Drosophila Arc

10.1101/2020.11.18.388496 ◽

2020 ◽

Cited By ~ 1

Author(s):

Erik I. Hallin ◽

Sigurbjörn Markússon ◽

Lev Böttger ◽

Andrew E. Torda ◽

Clive R. Bramham ◽

...

Keyword(s):

Synaptic Plasticity ◽

Brain Function ◽

Sequence Similarity ◽

Solution Structures ◽

Terminal Domain ◽

Large N ◽

Structural Homologues ◽

Mammalian Protein

AbstractSynaptic plasticity is vital for brain function and memory formation. One of the key proteins in long-term synaptic plasticity and memory is the activity-regulated cytoskeleton-associated protein (Arc). Mammalian Arc forms virus-like capsid-like structures in a process requiring the N-terminal domain and contains two C-terminal lobes that are structural homologues to retroviral capsids. Drosophila has two isoforms of Arc, dArc1 and dArc2, with low sequence similarity to mammalian Arc, but lacking the mammalian Arc N-terminal domain. Both dArc isoforms have a capsid homology domain consisting of N- and C-terminal lobes. We carried out structural characterization of the four individual dArc lobe domains. As opposed to the corresponding mammalian Arc lobe domains, which are monomeric, the dArc lobes were all oligomeric in solution, indicating a strong propensity for homophilic interactions. The N-lobe from dArc2 formed a domain-swapped dimer in the crystal structure, resulting in a novel dimer interaction that could be relevant for capsid assembly or other dArc functions. This domain-swapped structure resembles the dimeric protein C of flavivirus capsids, as well as the structure of histones dimers, domain-swapped transcription factors, and membrane-interacting BAK domains. The strong oligomerization properties of the isolated dArc lobe domains explain the ability of dArc to form capsids in the absence of any large N-terminal domain, in contrast to the mammalian protein.

Download Full-text

Efficient transcriptional silencing in Saccharomyces cerevisiae requires a heterochromatin histone acetylation pattern.

Molecular and Cellular Biology ◽

10.1128/mcb.16.8.4349 ◽

1996 ◽

Vol 16 (8) ◽

pp. 4349-4356 ◽

Cited By ~ 238

Author(s):

M Braunstein ◽

R E Sobel ◽

C D Allis ◽

B M Turner ◽

J R Broach

Keyword(s):

Saccharomyces Cerevisiae ◽

X Chromosome ◽

Transcriptional Silencing ◽

Histone H4 ◽

Amino Terminal ◽

Terminal Domain ◽

Histone H4 Acetylation ◽

Lysine Residues ◽

Amino Terminal Domain ◽

Acetylation Pattern

Heterochromatin in metazoans induces transcriptional silencing, as exemplified by position effect variegation in Drosophila melanogaster and X-chromosome inactivation in mammals. Heterochromatic DNA is packaged in nucleosomes that are distinct in their acetylation pattern from those present in euchromatin, although the role these differences play in the structure of heterochromatin or in the effects of heterochromatin on transcriptional activity is unclear. Here we report that, as observed in the facultative heterochromatin of the inactive X chromosome in female mammalian cells, histones H3 and H4 in chromatin spanning the transcriptionally silenced mating-type cassettes of the yeast Saccharomyces cerevisiae are hypoacetylated relative to histones H3 and H4 of transcriptionally active regions of the genome. By immunoprecipitation of chromatin fragments with antibodies specific for H4 acetylated at particular lysine residues, we found that only three of the four lysine residues in the amino-terminal domain of histone H4 spanning the silent cassettes are hypoacetylated. Lysine 12 shows significant acetylation levels. This is identical to the pattern of histone H4 acetylation observed in centric heterochromatin of D. melanogaster. These two observations provide additional evidence that the silent cassettes are encompassed in the yeast equivalent of metazoan heterochromatin. Further, mutational analysis of the amino-terminal domain of histone H4 in S. cerevisiae demonstrated that this observed pattern of histone H4 acetylation is required for transcriptional silencing. This result, in conjunction with prior mutational analyses of yeast histones H3 and H4, indicates that the particular pattern of nucleosome acetylation found in heterochromatin is required for its effects on transcription and is not simply a side effect of heterochromatin formation.

Download Full-text