Cyclin-dependent kinases (CDKs) are protein kinases characterized by needing a separate subunit - a cyclin - that provides domains essential for enzymatic activity. CDKs play important roles in the control of cell division and modulate transcription in response to several extra- and intracellular cues. The evolutionary expansion of the CDK family in mammals led to the division of CDKs into three cell-cycle-related subfamilies (Cdk1, Cdk4 and Cdk5) and five transcriptional subfamilies (Cdk7, Cdk8, Cdk9, Cdk11 and Cdk20). Unlike the prototypical Cdc28 kinase of budding yeast, most of these CDKs bind one or a few cyclins, consistent with functional specialization during evolution. This review summarizes how, although CDKs are traditionally separated into cell-cycle or transcriptional CDKs, these activities are frequently combined in many family members. Not surprisingly, deregulation of this family of proteins is a hallmark of several diseases, including cancer, and drug-targeted inhibition of specific members has generated very encouraging results in clinical trials.

/pdf/cyclin-dependent-kinases-1c14dmvasz.pdf

Cyclin-dependent kinases

Controlling the Elongation Phase of Transcription with P-TEFb

Recent years have witnessed a sea change in our understanding of transcription regulation: whereas traditional models focused solely on the events that brought RNA polymerase II (Pol II) to a gene promoter to initiate RNA synthesis, emerging evidence points to the pausing of Pol II during early elongation as a widespread regulatory mechanism in higher eukaryotes. Current data indicate that pausing is particularly enriched at genes in signal-responsive pathways. Here the evidence for pausing of Pol II from recent high-throughput studies will be discussed, as well as the potential interconnected functions of promoter-proximally paused Pol II.

Promoter-proximal pausing of RNA polymerase II: emerging roles in metazoans

The Many Pathways of RNA Degradation

Many chromatin features play critical roles in regulating gene expression. A complete understanding of gene regulation will require the mapping of specific chromatin features in small samples of cells at high resolution. Here we describe Cleavage Under Targets and Tagmentation (CUT&Tag), an enzyme-tethering strategy that provides efficient high-resolution sequencing libraries for profiling diverse chromatin components. In CUT&Tag, a chromatin protein is bound in situ by a specific antibody, which then tethers a protein A-Tn5 transposase fusion protein. Activation of the transposase efficiently generates fragment libraries with high resolution and exceptionally low background. All steps from live cells to sequencing-ready libraries can be performed in a single tube on the benchtop or a microwell in a high-throughput pipeline, and the entire procedure can be performed in one day. We demonstrate the utility of CUT&Tag by profiling histone modifications, RNA Polymerase II and transcription factors on low cell numbers and single cells.

/pdf/cut-tag-for-efficient-epigenomic-profiling-of-small-samples-m89qkhvxp9.pdf

CUT&Tag for efficient epigenomic profiling of small samples and single cells

Cracking the RNA polymerase II CTD code

RNA polymerase II (Pol II) transcribes genes that encode proteins and noncoding small nuclear RNAs (snRNAs). The carboxyl-terminal repeat domain (CTD) of the largest subunit of mammalian RNA Pol II, comprising tandem repeats of the heptapeptide consensus Tyr 1 -Ser 2 -Pro 3 -Thr 4 -Ser 5 -Pro 6 -Ser 7 , is required for expression of both gene types. We show that mutation of serine-7 to alanine causes a specific defect in snRNA gene expression. We also present evidence that phosphorylation of serine-7 facilitates interaction with the snRNA gene–specific Integrator complex. These findings assign a biological function to this amino acid and highlight a gene type–specific requirement for a residue within the CTD heptapeptide, supporting the existence of a CTD code.

https://science.sciencemag.org/content/sci/318/5857/1777.full.pdf

Serine-7 of the RNA Polymerase II CTD Is Specifically Required for snRNA Gene Expression

The C-terminal domain (CTD) of the large subunit of RNA polymerase (pol) II comprises conserved heptad repeats, and post-translational modification of the CTD regulates transcription and cotranscriptional RNA processing. Recently, the spatial patterns of modification of the CTD repeats have been investigated, and new functions of CTD modification have been revealed. In addition, there are new insights into the roles of the enzymes that decorate the CTD. We review these new findings and reassess the role of the pol II CTD in the regulation of gene expression.

The pol II CTD: new twists in the tail

https://www.cell.com/trends/genetics/pdf/S0168-9525(12)00046-7.pdf

Sylvain Egloff

Papers

Cracking the RNA polymerase II CTD code

Serine-7 of the RNA Polymerase II CTD Is Specifically Required for snRNA Gene Expression

The pol II CTD: new twists in the tail

Updating the RNA polymerase CTD code: adding gene-specific layers.

Ser7 phosphorylation of the CTD recruits the RPAP2 Ser5 phosphatase to snRNA genes.