Separation-of-function mutation in HPC2, a member of the HIR complex in S. cerevisiae, results in derepression of the histone genes but does not confer cryptic TATA phenotypes

Vishnoi, Nidhi; Flaherty, Kacie; Hancock, Leandria C.; Ferreira, Monica E.; Amin, Amit Dipak; Prochasson, Philippe

doi:10.1016/j.bbagrm.2011.07.004

Cited by 11 publications

(10 citation statements)

References 58 publications

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“…Although the HIR complex binds DNA with high affinity, it does not bind specifically to the histone promoters (Prochasson et al 2005). The HIR complex is presumably recruited to the histone promoter through interaction with an unidentified sequence-specific transcription factor, probably involving the N-terminal domain of Hpc2 (Vishnoi et al 2011).…”

Section: Negative Regulation Of the Histone Genesmentioning

confidence: 99%

Regulation of Histone Gene Expression in Budding Yeast

Eriksson¹,

Ganguli²,

Nagarajavel³

et al. 2012

Genetics

116

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We discuss the regulation of the histone genes of the budding yeast Saccharomyces cerevisiae. These include genes encoding the major core histones (H3, H4, H2A, and H2B), histone H1 (HHO1), H2AZ (HTZ1), and centromeric H3 (CSE4). Histone production is regulated during the cell cycle because the cell must replicate both its DNA during S phase and its chromatin. Consequently, the histone genes are activated in late G1 to provide sufficient core histones to assemble the replicated genome into chromatin. The major core histone genes are subject to both positive and negative regulation. The primary control system is positive, mediated by the histone gene-specific transcription activator, Spt10, through the histone upstream activating sequences (UAS) elements, with help from the major G1/S-phase activators, SBF (Swi4 cell cycle box binding factor) and perhaps MBF (MluI cell cycle box binding factor). Spt10 binds specifically to the histone UAS elements and contains a putative histone acetyltransferase domain. The negative system involves negative regulatory elements in the histone promoters, the RSC chromatin-remodeling complex, various histone chaperones [the histone regulatory (HIR) complex, Asf1, and Rtt106], and putative sequence-specific factors. The SWI/SNF chromatin-remodeling complex links the positive and negative systems. We propose that the negative system is a damping system that modulates the amount of transcription activated by Spt10 and SBF. We hypothesize that the negative system mediates negative feedback on the histone genes by histone proteins through the level of saturation of histone chaperones with histone. Thus, the negative system could communicate the degree of nucleosome assembly during DNA replication and the need to shut down the activating system under replication-stress conditions. We also discuss post-transcriptional regulation and dosage compensation of the histone genes.

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Section: Negative Regulation Of the Histone Genesmentioning

confidence: 99%

Regulation of Histone Gene Expression in Budding Yeast

Eriksson¹,

Ganguli²,

Nagarajavel³

et al. 2012

Genetics

116

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“…The CDI and CDII domains are required for the repression of histone genes and the stability of Hpc2 protein, respectively (24). Hpc2 carries additional HUN (Hpc2-UBN1) domain within residues 569–601, displaying 46% identity to the N-terminal corresponding domain (residues 132–167) of human UBN1 (Figure 5A).…”

Section: Resultsmentioning

confidence: 99%

Dissecting the roles of the histone chaperones reveals the evolutionary conserved mechanism of transcription-coupled deposition of H3.3

Song

Seol

Yang

et al. 2013

Nucleic Acids Research

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The mammalian genome encodes multiple variants of histone H3 including H3.1/H3.2 and H3.3. In contrast to H3.1/H3.2, H3.3 is enriched in the actively transcribed euchromatin and the telomeric heterochromatins. However, the mechanism for H3.3 to incorporate into the different domains of chromatin is not known. Here, taking the advantage of well-defined transcription analysis system of yeast, we attempted to understand the molecular mechanism of selective deposition of human H3.3 into actively transcribed genes. We show that there are systemic H3 substrate-selection mechanisms operating even in yeasts, which encode a single type of H3. Yeast HIR complex mediated H3-specific recognition specificity for deposition of H3.3 in the transcribed genes. A critical component of this process was the H3 A-IG code composed of amino acids 87, 89 and 90. The preference toward H3.3 was completely lost when HIR subunits were absent and partially suppressed by human HIRA. Asf1 allows the influx of H3, regardless of H3 type. We propose that H3.3 is introduced into the active euchromatin by targeting the recycling pathway that is mediated by HIRA (or HIR), and this H3-selection mechanism is highly conserved through the evolution. These results also uncover an unexpected role of RI chaperones in evolution of variant H3s.

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“…We had previously established that the C-terminal portion of Hpc2, containing both the HRD and the NHRD, physically interacts with Hir1 (37). Very recently, Prochasson and colleagues described that in budding yeast, a so called Conserved Domain II (CD II) in Hpc2, which corresponds to the motif that best aligns with the UBN1 NHRD in Figure 1, is as essential as the CD III region (corresponding to UBN1 HRD) for the association and integrity of the HIR complex (44). This data is consistent with our findings, suggesting that there is functional conservation between the NHRD and CD II regions in human and budding yeast.…”

Section: Discussionmentioning

confidence: 99%

Identification of an Ubinuclein 1 Region Required for Stability and Function of the Human HIRA/UBN1/CABIN1/ASF1a Histone H3.3 Chaperone Complex

et al. 2012

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The mammalian HIRA/UBN1/CABIN1/ASF1a (HUCA) histone chaperone complex deposits the histone H3 variant H3.3 into chromatin, and is linked to gene activation, repression and chromatin assembly in diverse cell contexts. We recently reported that a short N-terminal fragment of UBN1 containing amino acids 1–175 is necessary and sufficient for interaction with the WD repeats of HIRA, and attributed this interaction to a region from residues 120–175 that is highly conserved in a yeast ortholog Hpc2 and so termed the HRD for Hpc2-Related Domain. In this report, through a more comprehensive and refined biochemical and mutational analysis, we identify a smaller and more moderately conserved region within residues 41–77 of UBN1, that we term the NHRD, that is essential for interaction with the HIRA WD repeats; we further demonstrate that the HRD is dispensable for this interaction. We employ analytical ultracentrifugation studies to demonstrate that the NHRD of UBN1 and the WD repeats of HIRA form a tight 1:1 complex with a dissociation constant in the nanomolar range. Mutagenesis experiments identify several key residues in the NHRD that are required for interaction with the HIRA WD repeat domain, stability of the HUCA complex in vitro and in vivo and changes in chromatin organization in primary human cells. Together, these studies implicate the NHRD domain of UBN1 as being an essential region for HIRA interaction and chromatin organization by the HUCA complex.

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Separation-of-function mutation in HPC2, a member of the HIR complex in S. cerevisiae, results in derepression of the histone genes but does not confer cryptic TATA phenotypes

Cited by 11 publications

References 58 publications

Regulation of Histone Gene Expression in Budding Yeast

Regulation of Histone Gene Expression in Budding Yeast

Dissecting the roles of the histone chaperones reveals the evolutionary conserved mechanism of transcription-coupled deposition of H3.3

Identification of an Ubinuclein 1 Region Required for Stability and Function of the Human HIRA/UBN1/CABIN1/ASF1a Histone H3.3 Chaperone Complex

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