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Generating a Fractal Microstructure of Laminin-111 to Signal to Cells
Published on: September 28, 2020
Cell-type-specific interactions at regulatory motifs in the first intron of the lamin A gene
Puneeta Arora1, Bh Muralikrishna, Veena K Parnaik
1Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India.
Abstract:
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.
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