title: PU.1 expression is modulated by the balance of functional sense and antisense RNAs regulated by a shared cis-regulatory element.
abstract: The transcription factor PU.1 is an important regulator of hematopoiesis; precise expression levels are critical for normal hematopoietic development and suppression of leukemia. We show here that noncoding antisense RNAs are important modulators of proper dosages of PU.1. Antisense and sense RNAs are regulated by shared evolutionarily conserved cis-regulatory elements, and we can show that antisense RNAs inhibit PU.1 expression by modulating mRNA translation. We propose that such antisense RNAs will likely be important in the regulation of many genes and may be the reason for the large number of overlapping complementary transcripts with so far unknown function.
authors.affiliation: Harvard Institutes of Medicine, Harvard Stem Cell Institute, Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA.
authors.forename: Alexander K
authors.initials: AK
authors.lastname: Ebralidze
authors.forename: Florence C
authors.initials: FC
authors.lastname: Guibal
authors.forename: Ulrich
authors.initials: U
authors.lastname: Steidl
authors.forename: Pu
authors.initials: P
authors.lastname: Zhang
authors.forename: Sanghoon
authors.initials: S
authors.lastname: Lee
authors.forename: Boris
authors.initials: B
authors.lastname: Bartholdy
authors.forename: Meritxell Alberich
authors.initials: MA
authors.lastname: Jorda
authors.forename: Victoria
authors.initials: V
authors.lastname: Petkova
authors.forename: Frank
authors.initials: F
authors.lastname: Rosenbauer
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.forename: Tajhal
authors.initials: T
authors.lastname: Dayaram
authors.forename: Johanna
authors.initials: J
authors.lastname: Klupp
authors.forename: Karen B
authors.initials: KB
authors.lastname: O'Brien
authors.forename: Britta
authors.initials: B
authors.lastname: Will
authors.forename: Maarten
authors.initials: M
authors.lastname: Hoogenkamp
authors.forename: Katherine L B
authors.initials: KL
authors.lastname: Borden
authors.forename: Constanze
authors.initials: C
authors.lastname: Bonifer
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Tenen
mesh_terms: D000818:Animals; D002460:Cell Line; D018274:Electroporation; D015870:Gene Expression; D006098:Granulocytes / Q000166:cytology / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D018189:Immunomagnetic Separation; D019169:Jurkat Cells; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D008957:Models, Genetic; D014176:Protein Biosynthesis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D034622:RNA Interference; D016372:RNA, Antisense / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*; D013601:T-Lymphocytes / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics*; D014158:Transcription, Genetic; D020298:U937 Cells; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D011518:Proto-Oncogene Proteins; D016372:RNA, Antisense; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D015534:Trans-Activators; D000099232:Proto-Oncogene Protein Spi-1