title: ELL facilitates RNA polymerase II pause site entry and release.
abstract: Transcription is a multi-stage process that coordinates several steps within the transcription cycle including chromatin reorganization, RNA polymerase II recruitment, initiation, promoter clearance and elongation. Recent advances have identified the super elongation complex, containing the eleven-nineteen lysine-rich leukaemia (ELL) protein, as a key regulator of transcriptional elongation. Here we show that ELL has a diverse and kinetically distinct role before its assembly into the super elongation complex by stabilizing Pol II recruitment/initiation and entry into the pause site. Loss of ELL destabilizes the pre-initiation complexes and results in disruption of early elongation and promoter proximal chromatin structure before recruitment of AFF4 and other super elongation complex components. These changes result in significantly reduced transcriptional activation of rapidly induced genes. Thus, ELL has an early and essential role during rapid high-amplitude gene expression that is required for both Pol II pause site entry and release.
authors.affiliation: Laboratory of Receptor Biology and Gene Expression, National Cancer Institute, Bethesda, Maryland 20892, USA.
authors.forename: Jung S
authors.initials: JS
authors.lastname: Byun
authors.forename: Temesgen D
authors.initials: TD
authors.lastname: Fufa
authors.forename: Clay
authors.initials: C
authors.lastname: Wakano
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernandez
authors.forename: Cynthia M
authors.initials: CM
authors.lastname: Haggerty
authors.forename: Myong-Hee
authors.initials: MH
authors.lastname: Sung
authors.forename: Kevin
authors.initials: K
authors.lastname: Gardner
mesh_terms: D001665:Binding Sites; D002843:Chromatin / Q000737:chemistry; D047369:Chromatin Immunoprecipitation; D005786:Gene Expression Regulation; D057809:HEK293 Cells; D006657:Histones / Q000737:chemistry; D006801:Humans; D019169:Jurkat Cells; D007700:Kinetics; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D011401:Promoter Regions, Genetic; D034622:RNA Interference; D012319:RNA Polymerase II / Q000737:chemistry*; D014158:Transcription, Genetic; D035602:Transcriptional Elongation Factors / Q000378:metabolism*
chemical_list: D002843:Chromatin; C090862:ELL protein, human; D006657:Histones; D035602:Transcriptional Elongation Factors; D012319:RNA Polymerase II