Activation of the lamin A gene during rat liver development

Abstract

We have studied the regulation of expression of the Atype lamins, which are constituents of the nuclear lamina. During rat liver development, high levels of lamin A and C mRNAs were observed in 15-day fetal fiver but were barely detectable in the adult. The chromatin conformation of the lamin A gene was sensitive to DNase I in 15-day fetal liver but became mostly insensitive in the adult. Lamin A and C proteins could be detected in fetal liver and persisted in the adult. Our evidence suggests that the lamin A gene is actively transcribed early in fiver differentiation and its activity declines considerably in adult liver.Key words." Lamin A gene; Nuclear lamina; Liver development occurs primarily at the level of transcription. This differential gene expression in developing liver provides sufficient background for the study of regulatory mechanisms of other developmentally activated genes such as the A-type lamins.In order to understand how the lamin A gene is regulated, we have initially assessed lamin A expression during rat liver development by Northern analysis of RNA and nuclear runon transcription assays. The unfolding of the chromatin structure of the gene has been studied and lamin A protein levels determined. Our evidence suggests that the lamin A gene is actively transcribed by day 15 of embryonic liver development.

The Protein Composition of the Hepatocyte Nuclear Matrix Is Differentiation‐Stage Specific

“…4A, the relative concentration of lamin B in the nuclear matrices remained unchanged. In agreement with Hamid et al (18), and considerably earlier than reported previously (19), lamins A and C were already detectable in 16-day-old fetal livers (Fig. 4B, lane 1).…”

“…The A-type lamins increase with terminal differentiation and growth arrest, suggesting a role for A-type lamins in cellular quiescence (20). In light of the recently reported decrease in transcriptional activity of the lamin A gene in adult rats (18), the increased concentration of lamin A could be the result of its slower turnover. Apparently, expression of lamin A/C, not lamin B, correlates with the differentiation stage of the hepatocyte.…”

Functional Analysis of the 5′ Promoter Region of the Rat Lamin A Gene

“…We have observed that the -1877/+181 fragment of the rat lamin A promoter shows considerable activity in a mouse embryonal carcinoma cell line (PCC-4) (data not shown). We have earlier reported that this cell line does not express lamin A RNA (Hamid et al, 1996), which is consistent with several studies on lamin expression in embryonic cells. A possible interpretation of these findings is that the transiently transfected DNA does not acquire the repressed chromatin structure of the embryonic lamin A gene, and this structure is required for exclusion of ubiquitous transcription factors such as Spl and API.…”

“…Several studies have established that lamin A and C proteins are expressed only in differentiated cells and are not detectable in early embryos or undifferentiated embryonal carcinoma cell lines (Stewart and Burke, 1987;Rober et al, 1989;Lehner et al, 1987;Benavente et al, 1985;Stick and Hausen, 1985). The expression of the mammalian lamin A gene has been shown to be primarily under transcriptional control during embryonic liver development in the rat (Hamid et al, 1996) and on differentiation of embryonal carcinoma cells induced by retinoic acid (Mattia era/., 1992), although an instance of posttranscriptional control has been reported (Lanoix et al, 1992). The expression of Drosophila A-type lamin during development is also under transcriptional control (Riemer et al, 1995).…”

“…Moreover, maximal levels of lamin A RNAs are observed in dividing, differentiated cells, and these are reduced to barely detectable amounts in quiescent cells (Hamid et al, 1996;Parnaik et al, 1994). Hence, the extent of expression of the lamin A gene depends on both the growth and the differentiation status of the cell.…”