Cell-type-specific interactions at regulatory motifs in the first intron of the lamin A gene.
Lamins A, C and C2 are alternatively spliced products of the LMNA gene; lamins A and C are expressed in differentiated somatic cells, whereas lamin C2 is expressed in germ cells. We have analyzed a segment of the first intron of the LMNA gene for cell-type-specific regulatory elements. We identified a 420-bp fragment that increased promoter activity in lamin A-expressing cells but repressed activity in undifferentiated cells. DNase I footprinting and electrophoretic mobility shift assays revealed two binding motifs, footprinted region A (FPRA) and FPRB. The hepatocyte nuclear factor-3beta was bound to FPRA only in somatic cell extracts and this motif had an inhibitory effect on promoter activity. The retinoic X receptor beta, RXRbeta, bound near FPRB with extracts from lamin A- or C2-expressing cells, and this site enhanced promoter activity. We have, thus, identified two novel binding sites for transcription factors in a region likely to function as an important regulatory element for the cell-type-specific transcription of A-type lamins.
Arora
Puneeta
P
Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Muralikrishna
Bh
B
Parnaik
Veena K
VK
D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics / Q000378:metabolism; D018983:DNA Footprinting; D024202:Electrophoretic Mobility Shift Assay; D007438:Introns; D034904:Lamin Type A / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D012045:Regulatory Sequences, Nucleic Acid
D034904:Lamin Type A; D004247:DNA