Astrocyte- and hepatocyte-specific expression of genes from the distal serpin subcluster at 14q32.1 associates with tissue-specific chromatin structures.
The distal serpin subcluster contains genes encoding alpha1-antichymotrypsin (ACT), protein C inhibitor (PCI), kallistatin (KAL) and the KAL-like protein, which are expressed in hepatocytes, but only the act gene is expressed in astrocytes. We show here that the tissue-specific expression of these genes associates with astrocyte- and hepatocyte-specific chromatin structures. In hepatocytes, we identified 12 Dnase I-hypersensitive sites (DHSs) that were distributed throughout the entire subcluster, with the promoters of expressed genes accessible to restriction enzyme digestion. In astrocytes, only six DHSs were located exclusively in the 5' flanking region of the act gene, with its promoter also accessible to restriction enzyme digestion. The acetylation of histone H3 and H4 was found throughout the subcluster in both cell types but this acetylation did not correlate with the expression pattern of these serpin genes. Analysis of histone modifications at the promoters of the act and pci genes revealed that methylation of histone H3 on lysine 4 correlated with their expression pattern in both cell types. In addition, inhibition of methyltransferase activity resulted in suppression of ACT and PCI mRNA expression. We propose that lysine 4 methylation of histone H3 correlates with the tissue-specific expression pattern of these serpin genes.
Gopalan
Sunita
S
Department of Biochemistry, Medical College of Virginia Campus, Virginia Commonwealth University, Richmond, Virginia 23298, USA.
Kasza
Aneta
A
Xu
Weili
W
Kiss
Daniel L
DL
Wilczynska
Katarzyna M
KM
Rydel
Russell E
RE
Kordula
Tomasz
T
D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D015152:Blotting, Northern / Q000379:methods; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D002843:Chromatin / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation / Q000379:methods; D002874:Chromosome Mapping; D002883:Chromosomes, Human, Pair 14; D002918:Chymotrypsin / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003850:Deoxyribonuclease I / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D019901:Locus Control Region; D008239:Lysine / Q000378:metabolism; D008745:Methylation; D011401:Promoter Regions, Genetic; D018046:Protein C Inhibitor / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015842:Serine Proteinase Inhibitors / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection / Q000379:methods
D002352:Carrier Proteins; D002843:Chromatin; D016207:Cytokines; D006657:Histones; D018046:Protein C Inhibitor; D012333:RNA, Messenger; D015842:Serine Proteinase Inhibitors; D015843:Serpins; C051324:kallistatin; C094472:serpin B6; D003850:Deoxyribonuclease I; D002918:Chymotrypsin; C117608:alpha-chymotrypsin; D008239:Lysine