Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation

@article{Chlamydas2016FunctionalIB,
  title={Functional interplay between MSL1 and CDK7 controls RNA polymerase II Ser5 phosphorylation},
  author={Sarantis Chlamydas and Herbert Holz and Maria Samata and Tomasz Chelmicki and Plamen G. Georgiev and Vicent Pelechano and Friederike D{\"u}ndar and Pouria Dasmeh and Gerhard Mittler and Filipe Tavares Cadete and Fidel Ram{\'i}rez and Thomas Conrad and Wu Wei and Sunil Jayaramaiah Raja and Thomas Manke and Nicholas M. Luscombe and Lars M. Steinmetz and Asifa Akhtar},
  journal={Nature Structural \&Molecular Biology},
  year={2016},
  volume={23},
  pages={580-589}
}
Proper gene expression requires coordinated interplay among transcriptional coactivators, transcription factors and the general transcription machinery. We report here that MSL1, a central component of the dosage compensation complex in Drosophila melanogaster and Drosophila virilis, displays evolutionarily conserved sex-independent binding to promoters. Genetic and biochemical analyses reveal a functional interaction of MSL1 with CDK7, a subunit of the Cdk-activating kinase (CAK) complex of… Expand
RNA nucleation by MSL2 induces selective X chromosome compartmentalization
TLDR
It is shown that the low-complexity C-terminal domain (CTD) of MSL2 renders its recruitment to the X chromosome sensitive to roX non-coding RNAs, and the condensing nature of roX–MSL2 CTD is the primary determinant for specific compartmentalization of the X chromosomes in Drosophila. Expand
N-terminus of Drosophila MSL1 interacts with DNA-binding proteins and is critical for the recruitment of the dosage compensation complex to the X chromosome
TLDR
It is demonstrated that the N-terminal unstructured region of MSL1 interacts with many different DNA-binding proteins that contain clusters of the C2H2 zinc-finger domains that increase the specificity of DCC recruitment to the male X chromosome. Expand
Targeting of proteins to chromatin in Drosophila melanogaster
Dosage compensation of sex chromosomes in Drosophila melanogaster is an excellent model system to study various aspects of targeting of protein factors to chromatin. Dosage compensation prevents maleExpand
CLAMP directly interacts with MSL2 to facilitate Drosophila dosage compensation
TLDR
It is demonstrated that MSL2 directly interacts with the N-terminal zinc-finger domain of CLAMP, which is cooperatively involved in recruitment of MSL complex to the X chromosome. Expand
Intergenerationally Maintained Histone H4 Lysine 16 Acetylation Is Instructive for Future Gene Activation
TLDR
It is shown that histone H4 lysine 16 acetylation is maintained from oocytes to fertilized embryos in Drosophila and mammals, and maternal H4K16ac provides an instructive function to the offspring, priming future gene activation. Expand
Multi-step regulation of transcription kinetics explains the non-linear relation between RNA polymerase II density and mRNA expression in dosage compensation.
  • P. Dasmeh
  • Chemistry, Medicine
  • Journal of theoretical biology
  • 2018
TLDR
It is shown how multi-step enhancement of Pol II transcription can increase mRNA production while leaving Pol II densities unaffected, and points to erroneous interpretations ofPol II profiles from chromatin immunoprecipitation sequencing (ChIP-seq) or global run-on assays. Expand
Multi-step regulation of transcription kinetics explains the non-linear relation between RNA polymerase II density and mRNA expression in Dosage Compensation
TLDR
It is shown how multi-step enhancement of Pol II transcription can increase mRNA production while leaving Pol II densities unaffected, and a limitation of inferences based on Pol II profiles from chromatin immunoprecipitation sequencing (ChIP-seq) or global run-on assays is pointed to. Expand
Rapid Evolution of Autosomal Binding Sites of the Dosage Compensation Complex in Drosophila melanogaster and Its Association With Transcription Divergence
TLDR
It is found pervasive expansion of the MSL binding sites in D. melanogaster, particularly on autosomes, which points to an intriguing avenue of investigation of pleiotropy as a mechanism promoting rapid protein sequence evolution. Expand
Facultative dosage compensation of developmental genes on autosomes in Drosophila and mouse embryonic stem cells
TLDR
It is reported that MSL2, in addition to regulating the X chromosome, targets autosomal genes involved in patterning and morphogenesis, which maintains such regulation during evolution, as MSL 2 binds and similarly regulates mouse orthologues via Histone H4 lysine 16 acetylation. Expand
Faint gray bands in Drosophila melanogaster polytene chromosomes are formed by coding sequences of housekeeping genes
TLDR
In Drosophila melanogaster, the chromatin of interphase polytene chromosomes appears as alternating decondensed interbands and dense black or thin gray bands, and bioinformatic analysis indicates that in the X chromosome, it is only the lazurite chromatin that is simultaneously enriched for the proteins and histone marks associated with exons, transcription elongation, and dosage compensation. Expand
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References

SHOWING 1-10 OF 66 REFERENCES
Cdk7 Is Required for Full Activation of Drosophila Heat Shock Genes and RNA Polymerase II Phosphorylation In Vivo
TLDR
In vivo approaches revealed that Cdk7 kinase activity is required for full activation of heat shock genes, promoter-proximal Pol II pausing, and Pol II-dependent chromatin decondensation, and evidence that TFIIH associates with the elongation complex much longer than previously suspected is provided. Expand
Nuclear pore components are involved in the transcriptional regulation of dosage compensation in Drosophila.
TLDR
The purification of enzymatically active MSL complexes from Drosophila embryos, Schneider cells, and human HeLa cells reveals an unexpected physical and functional connection between nuclear pore components and chromatin regulation through MSL proteins, highlighting the role of nucleoporins in gene regulation in higher eukaryotes. Expand
Global Analysis of the Relationship between JIL-1 Kinase and Transcription
TLDR
It is hypothesised that one specific role of JIL-1 may be to reinforce, rather than to establish, the status of active chromatin through the phosphorylation of histone H3 at serine 10. Expand
MSL2 combines sensor and effector functions in homeostatic control of the Drosophila dosage compensation machinery.
TLDR
A new mechanism is described through which MSL2 can fulfill its role as the central regulator of the faithful biogenesis and functionality of the DC machinery, uncovering proteasome-dependent degradation as an additional layer of homeostatic control of MSL levels. Expand
The nonspecific lethal complex is a transcriptional regulator in Drosophila.
TLDR
The biochemical characterization of the nonspecific lethal (NSL) complex that associates with the histone acetyltransferase MOF in both Drosophila and mammals concludes that the NSL complex acts as a major transcriptional regulator in Drosophile. Expand
Cyclin-dependent kinase control of the initiation-to-elongation switch of RNA polymerase II
TLDR
It is shown that selective inhibition of Cdk7—part of TFIIH—increases TFIIE retention, prevents DRB sensitivity–inducing factor (DSIF) recruitment and attenuates pausing in human cells, which ensures gene-specific regulation and RNA quality control by Pol II. Expand
RNAP II CTD Phosphorylated on Threonine-4 Is Required for Histone mRNA 3′ End Processing
TLDR
Evidence is provided that phosphorylation of CTD Thr4 residues is required specifically for histone mRNA 3′ end processing, functioning to facilitate recruitment of 3′ processing factors to histone genes. Expand
Phosphorylation in transcription: the CTD and more.
TLDR
Summarizing the phosphorylation of various components of the transcription machinery, this work points out the variety of steps in transcription that are regulated by such protein modifications, envisioning an interconnection of the several stages of mRNA synthesis by phosphorylate. Expand
Targeting transcription regulation in cancer with a covalent CDK7 inhibitor
TLDR
The discovery and characterization of a covalent CDK7 inhibitor, THZ1, is presented, which has the unprecedented ability to target a remote cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity forCDK7. Expand
Genome-wide Analysis Reveals MOF as a Key Regulator of Dosage Compensation and Gene Expression in Drosophila
Dosage compensation, mediated by the MSL complex, regulates X-chromosomal gene expression in Drosophila. Here we report that the histone H4 lysine 16 (H4K16) specific histone acetyltransferase MOFExpand
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