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NURF Localizes in Gene Bodies to Regulate mRNA Processing
Author(s) -
Landry Joseph,
Alhazmi Aiman,
Mack Marissa,
Petencin Alexander,
Nelson Humberto,
Hiegel Jordan,
Koparde Vishal,
Scarsdale Neel,
Lyons Charles,
Dozmorov Mikhail
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1053.1
Subject(s) - biology , bromodomain , chromatin remodeling , phd finger , chromatin , rna polymerase ii , gene , genetics , gene expression , swi/snf , promoter , regulation of gene expression , intron , nucleosome , transcription factor , microbiology and biotechnology , histone , zinc finger
Understanding how chromatin remodeling complexes are recruited to chromatin is important to our understanding of how they regulate gene expression. Towards this end we determined the genome wide localization and sites of putative chromatin remodeling activity for the Nucleosome Remodeling Factor (NURF) by targeting its largest and essential subunit bromodomain PHD finger containing transcription factor (BPTF). From our BPTFChIP‐Seq and FAIRE‐Seq studies in BPTF knockout ESC we observe that BPTF islocalized and regulates chromatin structure broadly throughout the genome with a preference for promoters, gene bodies and terminators. A bio informatics analysis of these data sets discovers that a majority of NURF function as aregulator of gene expression is correlated with gene bodies and terminators. Abiochemical screen for binding partners of the BPTF N‐terminal PHD finger discovers specific interactions with THOC4, a mRNA processing factor which binds to an elongating polymerase. Analysis of NURF function at the BPTF‐dependent gene Ccnd1 discovers BPTF‐dependent roles in splicing out intronDNA sequences from mRNA transcripts. These defects correlate with evidence of RNA polymerase stalling, a known mechanism for down regulating gene expression with intron retention (IR). These results present model where NURF regulated gene expression can occurs through defects in retaining intron sequences. Support or Funding Information Jeffress Foundation Virginia Academy of Sciences Virginia Commonwealth University Massey Cancer Center