Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway

Mukiza, Tresor O.; Protacio, Reine U.; Davidson, Mari K.; Steiner, Walter W.; Wahls, Wayne P.

doi:10.1534/genetics.119.302679

Cited by 17 publications

(12 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This fact further supports the claim that phosphorylation of Atf1 by Sty1, either at the canonical S/TP sites or at so far unidentified residues, is the key molecular event causing activation of the TF. In all these genes/scenarios, Atf1 seems to be the only TF promoting transcription or recombination, and we propose that phosphorylation at canonical or non-canonical sites is sufficient to trigger a TF-mediated opening of the chromatin at those specific chromosomal locations, maybe by recruiting the Spt-Ada-Gcn5 acetyltransferase (SAGA) complex which has been demonstrated to regulate stress genes [48], ste11 [49] and recombination at ade6-M26 [38,50]. Another possibility, the Sty1-dependent modification of Atf1 by a mechanism other than phosphorylation, could also explain why Sty1 is required for the activity of Atf1.10M; nevertheless, enzymatic properties other than kinase have never been attributed to this family of enzymes.…”

Section: Discussionmentioning

confidence: 96%

Phosphorylation of the Transcription Factor Atf1 at Multiple Sites by the MAP Kinase Sty1 Controls Homologous Recombination and Transcription

Sánchez-Mir

Fraile

Ayté

et al. 2020

Journal of Molecular Biology

View full text Add to dashboard Cite

Transcription factors are often the downstream effectors of signaling cascades. In fission yeast, the transcription factor Atf1 is phosphorylated by the MAP kinase Sty1 under several environmental stressors to promote transcription initiation of stress genes. However, Sty1 and Atf1 have also been involved in other cellular processes such as homologous recombination at hotspots, ste11 gene expression during mating and meiosis, or regulation of fbp1 gene transcription under glucose starvation conditions. Using different phospho-mutants of Atf1, we have investigated the role of Atf1 phosphorylation by Sty1 in those biological processes. An Atf1 mutant lacking the canonical MAP kinase phosphorylation sites cannot activate fbp1 transcription when glucose is depleted, but it is still able to induce recombination at ade6.M26 and to induce ste11 after nitrogen depletion; in these last cases, Sty1 is still required, suggesting that additional non-canonical sites are activating the transcription factor. In all cases, an Atf1 phosphomimetic mutant bypasses the requirement of the Sty1 kinase in these diverse biological processes, highlighting the essential role of the DNA binding factor Atf1 on chromatin remodeling and cell adaptation to nutritional changes. We propose that posttranslational modifications of Atf1 by Sty1, either at canonical or non-canonical sites, are sufficient to activate some of the functions of Atf1, those involving chromatin remodelling and transcription initiation. However, in the case of fbp1 where Atf1 acts synergistically with other transcription factors, elimination of the canonical sites is sufficient to hamper some of the interactions required in this complex scenario and to impair transcription initiation.

show abstract

Section: Discussionmentioning

confidence: 96%

Phosphorylation of the Transcription Factor Atf1 at Multiple Sites by the MAP Kinase Sty1 Controls Homologous Recombination and Transcription

Sánchez-Mir

Fraile

Ayté

et al. 2020

Journal of Molecular Biology

View full text Add to dashboard Cite

show abstract

“…Fusion of Spo11 to Gal4-BD stimulates DSB formation at >200 sites in mice ( 56 ), and fusion of Spo11 to other DNA site-specific binding proteins, such as Cas9–sgRNA and zinc fingers, results in novel DSB and crossover hotspots in S. cerevisiae ( 63 ). In an alternative approach, introduction of the DNA sequence for binding of each of three transcription factors into the S. pombe ade6 gene results in recombination hotspots dependent on the respective endogenous (unfused) transcription factor ( 10 , 64 ). Similar to previous work in S. cerevisiae that tethered Ssp1, a subunit of the histone-methylating COMPASS complex, to Gal4-BD to create DSB hotspots ( 65 , 66 ), we have created hotspots using the LinE proteins that determine endogenous meiotic hotspots and act before DSB formation.…”

Section: Discussionmentioning

confidence: 99%

“…The determinants of DSB hotspots are not completely known in any case, but multiple factors, both DNA sequence and chromosome-bound proteins, contribute. The binding of certain transcription factors is a major determinant in some cases, but the individual transcription factors tested appear to account for only a small minority of hotspots across the genome ( 8 , 10 ). More general aspects of chromatin structure are also important.…”

Section: Introductionmentioning

confidence: 99%

Redirecting meiotic DNA break hotspot determinant proteins alters localized spatial control of DNA break formation and repair

Hyppa

Cho

Nambiar

et al. 2021

Nucleic Acids Research

View full text Add to dashboard Cite

During meiosis, DNA double-strand breaks (DSBs) are formed at high frequency at special chromosomal sites, called DSB hotspots, to generate crossovers that aid proper chromosome segregation. Multiple chromosomal features affect hotspot formation. In the fission yeast S. pombe the linear element proteins Rec25, Rec27 and Mug20 are hotspot determinants – they bind hotspots with high specificity and are necessary for nearly all DSBs at hotspots. To assess whether they are also sufficient for hotspot determination, we localized each linear element protein to a novel chromosomal site (ade6 with lacO substitutions) by fusion to the Escherichia coli LacI repressor. The Mug20-LacI plus lacO combination, but not the two separate lac elements, produced a strong ade6 DSB hotspot, comparable to strong endogenous DSB hotspots. This hotspot had unexpectedly low ade6 recombinant frequency and negligible DSB hotspot competition, although like endogenous hotspots it manifested DSB interference. We infer that linear element proteins must be properly placed by endogenous functions to impose hotspot competition and proper partner choice for DSB repair. Our results support and expand our previously proposed DSB hotspot-clustering model for local control of meiotic recombination.

show abstract

“…To convert the number of generations into historical time, we assume that one generation occurs every 25 years, on average. Both aforementioned formulas would not be accurate because meiotic recombination frequently occurs at the same hot-spot sites with short nucleotide consensuses [57]. In order to take this phenomenon into account, we added a calibration constant (C) into the two formulas, resulting in the following variations: L = C/(2 × g × r) and L = C/(g × r) respectively.…”

Section: Methodsmentioning

confidence: 99%

Global Picture of Genetic Relatedness and the Evolution of Humankind

Khvorykh

Mulyar²,

Fedorova³

et al. 2020

Biology

View full text Add to dashboard Cite

We performed an exhaustive pairwise comparison of whole-genome sequences of 3120 individuals, representing 232 populations from all continents and seven prehistoric people including archaic and modern humans. In order to reveal an intricate picture of worldwide human genetic relatedness, 65 million very rare single nucleotide polymorphic (SNP) alleles have been bioinformatically processed. The number and size of shared identical-by-descent (IBD) genomic fragments for every pair of 3127 individuals have been revealed. Over 17 million shared IBD fragments have been described. Our approach allowed detection of very short IBD fragments (<20 kb) that trace common ancestors who lived up to 200,000 years ago. We detected nine distinct geographical regions within which individuals had strong genetic relatedness, but with negligible relatedness between the populations of these regions. The regions, comprising nine unique genetic components for mankind, are the following: East and West Africa, Northern Europe, Arctica, East Asia, Oceania, South Asia, Middle East, and South America. The level of admixture in every studied population has been apportioned among these nine genetic components. Genetically, long-term neighboring populations are strikingly similar to each other in spite of any political, religious, and cultural differences. The topmost admixture has been observed at the center of Eurasia. These admixed populations (including Uyghurs, Azerbaijanis, Uzbeks, and Iranians) have roughly equal genetic contributions from the Middle East, Europe, China, and India, with additional significant traces from Africa and Arctic. The entire picture of relatedness of all the studied populations unfolds and presents itself in the form of shared number/size of IBDs.

show abstract

Diverse DNA Sequence Motifs Activate Meiotic Recombination Hotspots Through a Common Chromatin Remodeling Pathway

Abstract: Homologous recombination is induced to high levels in meiosis and is clustered at hotspots that regulate its frequency and distribution in the genome. By studying five different classes of DNA sequence-dependent recombination hotspots in the fission yeast...

Cited by 17 publications

References 74 publications

Phosphorylation of the Transcription Factor Atf1 at Multiple Sites by the MAP Kinase Sty1 Controls Homologous Recombination and Transcription

Phosphorylation of the Transcription Factor Atf1 at Multiple Sites by the MAP Kinase Sty1 Controls Homologous Recombination and Transcription

Redirecting meiotic DNA break hotspot determinant proteins alters localized spatial control of DNA break formation and repair

Global Picture of Genetic Relatedness and the Evolution of Humankind

Contact Info

Product

Resources

About