title: Mitotic Transcriptional Activation: Clearance of Actively Engaged Pol II via Transcriptional Elongation Control in Mitosis.
abstract: Although it is established that some general transcription factors are inactivated at mitosis, many details of mitotic transcription inhibition (MTI) and its underlying mechanisms are largely unknown. We have identified mitotic transcriptional activation (MTA) as a key regulatory step to control transcription in mitosis for genes with transcriptionally engaged RNA polymerase II (Pol II) to activate and transcribe until the end of the gene to clear Pol II from mitotic chromatin, followed by global impairment of transcription reinitiation through MTI. Global nascent RNA sequencing and RNA fluorescence in situ hybridization demonstrate the existence of transcriptionally engaged Pol II in early mitosis. Both genetic and chemical inhibition of P-TEFb in mitosis lead to delays in the progression of cell division. Together, our study reveals a mechanism for MTA and MTI whereby transcriptionally engaged Pol II can progress into productive elongation and finish transcription to allow proper cellular division.
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA; Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Kaiwei
authors.initials: K
authors.lastname: Liang
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA.
authors.forename: Ashley R
authors.initials: AR
authors.lastname: Woodfin
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Box
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA.
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Rickels
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Xin
authors.initials: X
authors.lastname: Gao
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Haug
authors.affiliation: Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA; Department of Molecular and Integrative Physiology, University of Kansas Medical Center, 3901 Rainbow Boulevard, Kansas City, KS 66160, USA.
authors.forename: Sue L
authors.initials: SL
authors.lastname: Jaspersen
authors.affiliation: Department of Biochemistry and Molecular Genetics, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA; Stowers Institute for Medical Research, 1000 E. 50th Street, Kansas City, MO 64110, USA; Robert H. Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, 320 E. Superior Street, Chicago, IL 60611, USA. Electronic address: ash@northwestern.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Shilatifard
mesh_terms: D004257:DNA Polymerase II / Q000378:metabolism*; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism*; D061805:Transcription Elongation, Genetic / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D042925:Positive Transcriptional Elongation Factor B; D004257:DNA Polymerase II