PMID- 17636019
OWN - NLM
STAT- MEDLINE
DCOM- 20080122
LR  - 20220317
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 27
IP  - 19
DP  - 2007 Oct
TI  - Epigenetic regulation of protein-coding and microRNA genes by the 
      Gfi1-interacting tumor suppressor PRDM5.
PG  - 6889-902
AB  - Gfi1 transcriptionally governs hematopoiesis, and its mutations produce 
      neutropenia. In an effort to identify Gfi1-interacting proteins and also to 
      generate new candidate genes causing neutropenia, we performed a yeast two-hybrid 
      screen with Gfi1. Among other Gfi1-interacting proteins, we identified a 
      previously uncharacterized member of the PR domain-containing family of tumor 
      suppressors, PRDM5. PRDM5 has 16 zinc fingers, and we show that it acts as a 
      sequence-specific, DNA binding transcription factor that targets 
      hematopoiesis-associated protein-coding and microRNA genes, including many that 
      are also targets of Gfi1. PRDM5 epigenetically regulates transcription similarly 
      to Gfi1: it recruits the histone methyltransferase G9a and class I histone 
      deacetylases to its target gene promoters and demonstrates repressor activity on 
      synthetic reporters; on endogenous target genes, however, it functions as an 
      activator, in addition to a repressor. Interestingly, genes that PRDM5 activates, 
      as opposed to those it represses, are also targets of Gfi1, suggesting a 
      competitive mechanism through which two repressors could cooperate in order to 
      become transcriptional activators. In neutropenic patients, we identified PRDM5 
      protein sequence variants perturbing transcriptional function, suggesting a 
      potentially important role in hematopoiesis.
FAU - Duan, Zhijun
AU  - Duan Z
AD  - Division of Medical Genetics, Department of Medicine, University of Washington 
      School of Medicine, Seattle, WA 98195, USA.
FAU - Person, Richard E
AU  - Person RE
FAU - Lee, Hu-Hui
AU  - Lee HH
FAU - Huang, Shi
AU  - Huang S
FAU - Donadieu, Jean
AU  - Donadieu J
FAU - Badolato, Raffaele
AU  - Badolato R
FAU - Grimes, H Leighton
AU  - Grimes HL
FAU - Papayannopoulou, Thalia
AU  - Papayannopoulou T
FAU - Horwitz, Marshall S
AU  - Horwitz MS
LA  - eng
GR  - R01 HL079507/HL/NHLBI NIH HHS/United States
GR  - CA112405/CA/NCI NIH HHS/United States
GR  - R01 HL079574/HL/NHLBI NIH HHS/United States
GR  - R01 CA112405/CA/NCI NIH HHS/United States
GR  - DK58161/DK/NIDDK NIH HHS/United States
GR  - HL079574/HL/NHLBI NIH HHS/United States
GR  - HL79507/HL/NHLBI NIH HHS/United States
GR  - R01 DK058161/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20070716
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (GFI1 protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (PRDM5 protein, human)
RN  - 0 (Transcription Factors)
RN  - EC 2.1.1.- (Histone Methyltransferases)
RN  - EC 2.1.1.- (Protein Methyltransferases)
RN  - EC 2.1.1.43 (Histone-Lysine N-Methyltransferase)
RN  - EC 3.5.1.98 (HDAC1 protein, human)
RN  - EC 3.5.1.98 (Histone Deacetylase 1)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
MH  - Cell Cycle/physiology
MH  - Cell Line
MH  - DNA-Binding Proteins/genetics/*metabolism
MH  - *Epigenesis, Genetic
MH  - *Gene Expression Regulation
MH  - Hematopoiesis/physiology
MH  - Histone Deacetylase 1
MH  - Histone Deacetylases/genetics/metabolism
MH  - Histone Methyltransferases
MH  - Histone-Lysine N-Methyltransferase/metabolism
MH  - Humans
MH  - MicroRNAs/*genetics/metabolism
MH  - Molecular Sequence Data
MH  - Neutropenia/genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Methyltransferases
MH  - RNA Interference
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - Two-Hybrid System Techniques
MH  - Zinc Fingers
PMC - PMC2099216
EDAT- 2007/07/20 09:00
MHDA- 2008/01/23 09:00
PMCR- 2008/02/01
CRDT- 2007/07/20 09:00
PHST- 2007/07/20 09:00 [pubmed]
PHST- 2008/01/23 09:00 [medline]
PHST- 2007/07/20 09:00 [entrez]
PHST- 2008/02/01 00:00 [pmc-release]
AID - MCB.00762-07 [pii]
AID - 0762-07 [pii]
AID - 10.1128/MCB.00762-07 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2007 Oct;27(19):6889-902. doi: 10.1128/MCB.00762-07. Epub 2007 Jul 
      16.