PMID- 15831451
OWN - NLM
STAT- MEDLINE
DCOM- 20050614
LR  - 20220317
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 25
IP  - 9
DP  - 2005 May
TI  - Adult stage gamma-globin silencing is mediated by a promoter direct repeat 
      element.
PG  - 3443-51
AB  - The human beta-like globin genes (5'-epsilon-Ggamma-Agamma-delta-beta-3') are 
      temporally expressed in sequential order from the 5' to 3' end of the locus, but 
      the nonadult epsilon- and gamma-globin genes are autonomously silenced in adult 
      erythroid cells. Two cis elements have been proposed to regulate definitive 
      erythroid gamma-globin repression: the DR (direct repeat) and CCTTG elements. 
      Since these two elements partially overlap, and since a well-characterized HPFH 
      point mutation maps to an overlapping nucleotide, it is not clear if both or only 
      one of the two participate in gamma-globin silencing. To evaluate the 
      contribution of these hypothetical silencers to gamma-globin regulation, we 
      generated point mutations that individually disrupted either the single DR or all 
      four CCTTG elements. These two were separately incorporated into human 
      beta-globin yeast artificial chromosomes, which were then used to generate 
      gamma-globin mutant transgenic mice. While DR element mutation led to a dramatic 
      increase in Agamma-globin expression only during definitive erythropoiesis, the 
      CCTTG mutation did not affect adult stage transcription. These results 
      demonstrate that the DR sequence element autonomously mediates definitive 
      stage-specific gamma-globin gene silencing.
FAU - Omori, Akane
AU  - Omori A
AD  - Graduate School of Life and Environmental Sciences, University of Tsukuba, 
      Tennoudai 1-1-1, Tsukuba, Ibaraki 305-8577, Japan.
FAU - Tanabe, Osamu
AU  - Tanabe O
FAU - Engel, James Douglas
AU  - Engel JD
FAU - Fukamizu, Akiyoshi
AU  - Fukamizu A
FAU - Tanimoto, Keiji
AU  - Tanimoto K
LA  - eng
GR  - R01 HL024415/HL/NHLBI NIH HHS/United States
GR  - R01 HL073465/HL/NHLBI NIH HHS/United States
GR  - HL 24415/HL/NHLBI NIH HHS/United States
GR  - HL 73465/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 9004-22-2 (Globins)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Chromosomes, Artificial, Yeast/genetics
MH  - Erythroid Cells/metabolism
MH  - Erythropoiesis/genetics/physiology
MH  - *Gene Expression Regulation, Developmental
MH  - *Gene Silencing
MH  - Globins/*genetics
MH  - Humans
MH  - Mice
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Point Mutation/genetics
MH  - Promoter Regions, Genetic/genetics/*physiology
MH  - Repetitive Sequences, Nucleic Acid/genetics/*physiology
MH  - Response Elements/genetics/*physiology
MH  - Transcription, Genetic/genetics/physiology
PMC - PMC1084292
EDAT- 2005/04/16 09:00
MHDA- 2005/06/15 09:00
PMCR- 2005/05/01
CRDT- 2005/04/16 09:00
PHST- 2005/04/16 09:00 [pubmed]
PHST- 2005/06/15 09:00 [medline]
PHST- 2005/04/16 09:00 [entrez]
PHST- 2005/05/01 00:00 [pmc-release]
AID - 25/9/3443 [pii]
AID - 1591-04 [pii]
AID - 10.1128/MCB.25.9.3443-3451.2005 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2005 May;25(9):3443-51. doi: 10.1128/MCB.25.9.3443-3451.2005.