PMID- 15892717
OWN - NLM
STAT- MEDLINE
DCOM- 20050928
LR  - 20161021
IS  - 0893-5785 (Print)
IS  - 0893-5785 (Linking)
VI  - 18
IP  - 3
DP  - 2005 Jun
TI  - Dynamic regulation of the human dopachrome tautomerase promoter by MITF, ER-alpha 
      and chromatin remodelers during proliferation and senescence of human 
      melanocytes.
PG  - 203-13
AB  - Senescent cells are known to display altered gene expression of 
      differentiation-associated genes. We have previously demonstrated that the 
      melanocyte transcriptional regulator microphthalmia-associated protein (MITF) is 
      down-regulated in senescent melanocytes. Since virtually nothing is known 
      regarding the differentiated function of senescent melanocytes, we analyzed the 
      transcriptional regulation of Dopachrome tautomerase (DCT), a member of the 
      tyrosinase gene family, in proliferating and in senescent human melanocytes. 
      Computational analysis of the region containing the M-box that includes the MITF 
      CATGTG binding motif demonstrated that this sequence overlaps with the estrogen 
      receptor alpha (ER-alpha), USF-1, TFE-3, Isl-1 and AP-1 binding elements. 
      Electrophoresis gel-shift analysis using an oligonucleotide containing MITF and 
      ERE elements identified MITF and ER-alpha complexes in proliferating melanocytes, 
      whereas only ER-alpha complexes were detected in senescent cells. Importantly, a 
      promoter-reporter analysis demonstrated that the coactivator p300/CBP switched 
      MITF from a repressor to an activator of DCT transcription. p300/CBP was also 
      required by ER-alpha and MITF to induce high, synergistic activation of the DCT 
      promoter. We have also found that transcription of the DCT gene is differentially 
      regulated by major melanocyte mitogens. In contrast to the activating effect of 
      cAMP inducers, 12-O-tetradecanoylphorbolacetate (TPA) was a potent repressor of 
      DCT transcription, suggesting that this gene can be differentially regulated by 
      multiple environmental signals and promoter context. In support of this 
      conclusion, trichostatin A, a histone deacetylase inhibitor, counteracted the 
      TPA-mediated repression, and restored high levels of DCT protein in cultured 
      melanocytes. We conclude that senescent melanocytes display dramatic changes in 
      the expression of differentiation-related proteins; such changes may in turn 
      result in altered melanocyte function and survival to environmental stresses.
FAU - Schwahn, Denise J
AU  - Schwahn DJ
AD  - Departmentsof Molecular and Cellular Biology, Baylor College of Medicine, 
      Houston, TX 77030, USA.
FAU - Timchenko, Nikolai A
AU  - Timchenko NA
FAU - Shibahara, Shigeki
AU  - Shibahara S
FAU - Medrano, Estela E
AU  - Medrano EE
LA  - eng
GR  - 1P01 AG19254/AG/NIA 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  - Denmark
TA  - Pigment Cell Res
JT  - Pigment cell research
JID - 8800247
RN  - 0 (Chromatin)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (MITF protein, human)
RN  - 0 (Microphthalmia-Associated Transcription Factor)
RN  - 0 (Transcription Factors)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.3.12 (dopachrome isomerase)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Cell Proliferation/drug effects
MH  - Chromatin/*metabolism
MH  - DNA-Binding Proteins/*metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Estrogen Receptor alpha/*metabolism
MH  - Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Intramolecular Oxidoreductases/antagonists & inhibitors/*genetics/metabolism
MH  - Melanocytes/cytology/drug effects/*metabolism
MH  - Microphthalmia-Associated Transcription Factor
MH  - Promoter Regions, Genetic/drug effects/genetics/*physiology
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/*metabolism
EDAT- 2005/05/17 09:00
MHDA- 2005/09/29 09:00
CRDT- 2005/05/17 09:00
PHST- 2005/05/17 09:00 [pubmed]
PHST- 2005/09/29 09:00 [medline]
PHST- 2005/05/17 09:00 [entrez]
AID - PCR229 [pii]
AID - 10.1111/j.1600-0749.2005.00229.x [doi]
PST - ppublish
SO  - Pigment Cell Res. 2005 Jun;18(3):203-13. doi: 10.1111/j.1600-0749.2005.00229.x.