A chromatin-based mechanism for limiting divergent noncoding transcription

TY - JOUR

T1 - A chromatin-based mechanism for limiting divergent noncoding transcription

AU - Marquardt, Sebastian

AU - Escalante-Chong, Renan

AU - Pho, Nam

AU - Wang, Jue

AU - Churchman, L Stirling

AU - Springer, Michael

AU - Buratowski, Stephen

N1 - Copyright © 2014 Elsevier Inc. All rights reserved.

PY - 2014/6/19

Y1 - 2014/6/19

N2 - In addition to their annotated transcript, many eukaryotic mRNA promoters produce divergent noncoding transcripts. To define determinants of divergent promoter directionality, we used genomic replacement experiments. Sequences within noncoding transcripts specified their degradation pathways, and functional protein-coding transcripts could be produced in the divergent direction. To screen for mutants affecting the ratio of transcription in each direction, a bidirectional fluorescent protein reporter construct was introduced into the yeast nonessential gene deletion collection. We identified chromatin assembly as an important regulator of divergent transcription. Mutations in the CAF-I complex caused genome-wide derepression of nascent divergent noncoding transcription. In opposition to the CAF-I chromatin assembly pathway, H3K56 hyperacetylation, together with the nucleosome remodeler SWI/SNF, facilitated divergent transcription by promoting rapid nucleosome turnover. We propose that these chromatin-mediated effects control divergent transcription initiation, complementing downstream pathways linked to early termination and degradation of the noncoding RNAs.

AB - In addition to their annotated transcript, many eukaryotic mRNA promoters produce divergent noncoding transcripts. To define determinants of divergent promoter directionality, we used genomic replacement experiments. Sequences within noncoding transcripts specified their degradation pathways, and functional protein-coding transcripts could be produced in the divergent direction. To screen for mutants affecting the ratio of transcription in each direction, a bidirectional fluorescent protein reporter construct was introduced into the yeast nonessential gene deletion collection. We identified chromatin assembly as an important regulator of divergent transcription. Mutations in the CAF-I complex caused genome-wide derepression of nascent divergent noncoding transcription. In opposition to the CAF-I chromatin assembly pathway, H3K56 hyperacetylation, together with the nucleosome remodeler SWI/SNF, facilitated divergent transcription by promoting rapid nucleosome turnover. We propose that these chromatin-mediated effects control divergent transcription initiation, complementing downstream pathways linked to early termination and degradation of the noncoding RNAs.

KW - Chromatin

KW - Chromatin Assembly Factor-1

KW - Chromatin Assembly and Disassembly

KW - Gene Expression Regulation, Fungal

KW - Nucleosomes

KW - Promoter Regions, Genetic

KW - RNA Stability

KW - RNA, Fungal

KW - RNA, Untranslated

KW - Saccharomyces cerevisiae

KW - Saccharomyces cerevisiae Proteins

KW - Transcription Termination, Genetic

KW - Transcription, Genetic

KW - Journal Article

KW - Research Support, N.I.H., Extramural

KW - Research Support, Non-U.S. Gov't

U2 - 10.1016/j.cell.2014.04.036

DO - 10.1016/j.cell.2014.04.036

M3 - Journal article

C2 - 24949978

SN - 0092-8674

VL - 157

SP - 1712

EP - 1723

JO - Cell

JF - Cell

IS - 7

ER -