Linker Histone H1.2 Cooperates with Cul4A and PAF1 to Drive H4K31 Ubiquitylation-Mediated Transactivation

Kim, Kyung-Hwan; Lee, Bomi; Kim, Jae-Hoon; Choi, Jinah; Kim, Jin Man; Xiong, Yue; Roeder, Robert G.; An, Woojin

doi:10.1016/j.celrep.2013.11.038

Cited by 58 publications

(71 citation statements)

References 45 publications

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“…As the name suggests, the PAF1C physically interacts with Pol II (3,4), and a previous study showed that a Paf1-Leo1 subcomplex of the PAF1C is responsible for its association with Pol II (14). Moreover, a few recent papers have revealed that the PAF1C directly interacts with histones (26,48). In the study by Kim et al (48), for example, the PAF1C was identified as an isoform-specific interactor of linker histone H1.2.…”

Section: Discussionmentioning

confidence: 98%

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Cao

Yamamoto

Isobe

et al. 2015

Molecular and Cellular Biology

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bRestores TBP function 1 (Rtf1) is generally considered to be a subunit of the Paf1 complex (PAF1C), a multifunctional protein complex involved in histone modification and transcriptional or posttranscriptional regulation. Rtf1, however, is not stably associated with the PAF1C in most species except Saccharomyces cerevisiae, and its biochemical functions are not well understood. Here, we show that human Rtf1 is a transcription elongation factor that may function independently of the PAF1C. Rtf1 requires "Rtf1 coactivator" activity, which is most likely unrelated to the PAF1C or DSIF, for transcriptional activation in vitro. A mutational study revealed that the Plus3 domain of human Rtf1 is critical for its coactivator-dependent function. Transcriptome sequencing (RNA-seq) and chromatin immunoprecipitation studies in HeLa cells showed that Rtf1 and the PAF1C play distinct roles in regulating the expression of a subset of genes. Moreover, contrary to the finding in S. cerevisiae, the PAF1C was apparently recruited to the genes examined in an Rtf1-independent manner. The present study establishes a role for human Rtf1 as a transcription elongation factor and highlights the similarities and differences between the S. cerevisiae and human Rtf1 proteins. Restores TBP (TATA box-binding protein) function 1 (Rtf1) was identified as a suppressor of a TBP mutant in Saccharomyces cerevisiae (1). Subsequent genetic and biochemical studies in yeast have shown that Rtf1 functions as a component of the polymerase-associated factor 1 (Paf1) complex (PAF1C) containing Paf1, Ctr9, Leo1, and Cdc73 (2-5). The PAF1C is a multifunctional protein complex whose primary role is to facilitate histone modifications, such as H2B monoubiquitination at K123 and H3 methylation at K4 and K79 (6-12). The PAF1C also plays important roles in transcription elongation through chromatin, as well as on naked DNA (13-16). Furthermore, the PAF1C is involved in transcription termination and 3= processing of polyadenylated and nonpolyadenylated .Paf1, Ctr9, Leo1, Cdc73, and Rtf1 are highly conserved in eukaryotes; however, the subunit compositions of the PAF1C vary among species. Purification of the PAF1C from human HeLa cells yielded a five-subunit complex lacking Rtf1 but containing Ski8 as an additional subunit (22,26,27). Similarly, coimmunoprecipitation studies in zebrafish, Drosophila, and Schizosaccharomyces pombe showed that PAF1C homologs in these species lack a stably associated Rtf1 subunit (28-30). At the functional level, however, Rtf1 and other PAF1C subunits have a number of similarities. For example, knockout or knockdown of Rtf1 and other PAF1C subunits results in similar defects in histone modifications in all the species examined (27,28,31). At the organismal level, inhibition of Rtf1 and other PAF1C subunits causes similar defects in epidermal morphogenesis in Caenorhabditis elegans and in somitogenesis and cardiomyocyte development in zebrafish (29,32,33). Rtf1 and Paf1 colocalize with each other and with RNA polymerase II (RNAPII) in...

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Section: Discussionmentioning

confidence: 98%

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Cao

Yamamoto

Isobe

et al. 2015

Molecular and Cellular Biology

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“…Interestingly, H1X was first found in a two-hybrid screen with the WD40 repeat region of the transcription factor TFIID as the bait (64), although this association was not further explored functionally. In relation to this, it has recently been described that H1.2 functionally interacts with Cul4A E3 ubiquitin ligase, PAF1 elongation complexes, and the serine 2-phosphorylated form of RNAPII that potentiates core histone modifications and targets gene transcriptional elongation in HeLa cells (65). Moreover, in the same study, WDR5, a substrate adaptor for Cul4A E3 ligase, was found to co-purify with six of the somatic H1 variants (H1.0 to H1.5); H1X was not explored.…”

Section: H1x Associates With Rnapii-enriched Regions Included Exonsmentioning

confidence: 99%

Genome Distribution of Replication-independent Histone H1 Variants Shows H1.0 Associated with Nucleolar Domains and H1X Associated with RNA Polymerase II-enriched Regions

Mayor¹,

Izquierdo‐Bouldstridge²,

Millán-Ariño³

et al. 2015

Journal of Biological Chemistry

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Background: There are seven histone H1 variants in somatic mammalian cells, two of which are replication-independent, H1.0 and H1X. Results: In breast cancer cells, H1.0 is enriched at nucleolus-associated domains, whereas H1X is associated with RNA polymerase II-enriched regions. Conclusion: Most H1 variants show great redundancy across the genome, but there is also some specificity. Significance: Some H1 variants may have specific functions.Unlike core histones, the linker histone H1 family is more evolutionarily diverse, and many organisms have multiple H1 variants or subtypes. In mammals, the H1 family includes seven somatic H1 variants; H1.1 to H1.5 are expressed in a replicationdependent manner, whereas H1.0 and H1X are replication-independent. Using ChIP-sequencing data and cell fractionation, we have compared the genomic distribution of H1.0 and H1X in human breast cancer cells, in which we previously observed differential distribution of H1.2 compared with the other subtypes. We have found H1.0 to be enriched at nucleolus-associated DNA repeats and chromatin domains, whereas H1X is associated with coding regions, RNA polymerase II-enriched regions, and hypomethylated CpG islands. Further, H1X accumulates within constitutive or included exons and retained introns and toward the 3 end of expressed genes. Inducible H1X knockdown does not affect cell proliferation but dysregulates a subset of genes related to cell movement and transport. In H1X-depleted cells, the promoters of up-regulated genes are not occupied specifically by this variant, have a lower than average H1 content, and, unexpectedly, do not form an H1 valley upon induction. We conclude that H1 variants are not distributed evenly across the genome and may participate with some specificity in chromatin domain organization or gene regulation.There are five major classes of histones that participate in the correct folding of eukaryotic DNA into chromatin: the core histones H2A, H2B, H3, and H4, which form an octamer and constitute the nucleosome core particle, and the linker histone H1, which binds to the nucleosomes near the entry/exit sites of linker DNA. Stabilization of the condensed states of chromatin is the function most commonly attributed to the linker histone (1, 2), in addition to its inhibitory effect in vitro on nucleosome mobility (3) and transcription (4).Histone H1 in humans is a family of closely related, single gene-encoded proteins, including seven somatic subtypes (H1.1 to H1.5, H1.0, and H1X), three testis-specific variants (H1t, H1T2, and HILS1), and one restricted to oocytes (H1oo) (5, 6). Among the somatic histone H1 variants, H1.1 to H1.5 are expressed in a replication-dependent manner, whereas H1.0 and H1X are replication-independent. The H1.1 to H1.5-encoding genes are clustered in a region of chromosome 6 together with the core histone genes, whereas the H1X and H1.0 genes are on chromosomes 3 and 22, respectively. H1.2 to H1.5 and H1X are ubiquitously expressed, H1.1 is restricted to certain tissues, and H1.0 accumulat...

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“…Non-proteolytic protein ubiquitylation, or mono-ubiquitylation, occurs on histones H2A, H2B, and H4 to regulate gene transcription (Geng et al, 2012;Kim et al, 2013). The major mono-ubiquitylation site in histone H2B is K123 in budding yeast, K119 in fission yeast and K120 and K34 in mammals (Cao and Yan, 2012;Fuchs and Oren, 2014).…”

Section: Rnapii Ctd and Histone Ubiquitylationmentioning

confidence: 99%

Modifications of RNA polymerase II CTD: Connections to the histone code and cellular function

Srivastava

Ahn

2015

Biotechnology Advances

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Linker Histone H1.2 Cooperates with Cul4A and PAF1 to Drive H4K31 Ubiquitylation-Mediated Transactivation

Cited by 58 publications

References 45 publications

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Characterization of the Human Transcription Elongation Factor Rtf1: Evidence for Nonoverlapping Functions of Rtf1 and the Paf1 Complex

Genome Distribution of Replication-independent Histone H1 Variants Shows H1.0 Associated with Nucleolar Domains and H1X Associated with RNA Polymerase II-enriched Regions

Modifications of RNA polymerase II CTD: Connections to the histone code and cellular function

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