Cell Type-specific Transcription of the α1(VI) Collagen Gene

Fabbro, Carla; Braghetta, Paola; Girotto, Davide; Piccolo, Stefano; Volpin, Dino; Bressan, Giorgio M.

doi:10.1074/jbc.274.3.1759

Cited by 14 publications

(8 citation statements)

References 31 publications

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“…6, b and c). As previously observed, one, indicated by * in the figure, was an invariant site present in all cells, whereas a second site, HS1, mapping at about Ϫ0.1 kb, was detectable in all cells expressing ␣1(VI) mRNA (10). Two other sites (HS2 and HS3) mapped at about Ϫ4.6 and Ϫ4.4 kb and were located within segments E-I and I-L, respectively (Figs.…”

Section: Chromatin Dnase I Footprinting Assayssupporting

confidence: 52%

“…Other Assays-Northern blotting, DNase I footprinting, identification of chromatin DNase I-hypersensitive sites, and electrophoretic mobility shift assays were performed exactly as described (7,10).…”

Section: Methodsmentioning

confidence: 99%

“…Our group has undertaken the study of regulation of collagen VI in the mouse and has identified several sequences of the 5Ј-flanking region of the Col6a1 gene active in transcriptional control (7)(8)(9)(10). In particular, analyses in transgenic mice have located three regions responsible for tissue-specific transcription at high frequency (8).…”

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confidence: 99%

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Analysis of Transcription of the Col6a1 Gene in a Specific Set of Tissues Suggests a New Variant of Enhancer Region

Girotto

Fabbro

Braghetta

et al. 2000

Journal of Biological Chemistry

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The region extending from ؊5.4 to ؊3.9 kilobase pairs from the transcription start site of the Col6a1 gene has been previously shown to contain sequences activating tissue-specific transcription in articular cartilage, intervertebral disks, subepidermal, and vibrissae mesenchyme and peripheral nervous system (Braghetta, P., Fabbro, C., Piccolo, S., Marvulli, D., Bonaldo, P., Volpin, D., and Bressan, G. M. (1996) J. Cell Biol. 135, 1163-1177). Analysis of expression of deletions of this region in transgenic mice has identified the 383-base pair fragment E-L as the most active sequence of the region. Linker-scanning mutagenesis analysis of segment E-J, which spans the 5 245 base pairs of E-L and is sufficient for high frequency expression in articular cartilage, showed that all the mutations reduced transcription considerably, suggesting that the integrity of the entire cluster of elements is necessary for enhancer activity. Electrophoretic mobility shift assays with nuclear extracts derived from various sources showed that fragment E-J binds numerous transcription factors (at least 22). These factors are present in most cells, expressing and nonexpressing ␣1(VI) collagen mRNA, but in different relative proportions, and none of them appears to be cell type-specific. Several lines of evidence indicate that sequence elements of the enhancer may have different functional roles in various cells. The data configure the ؊5.4/؊3.9 region of the Col6a1 gene as a new type of tissue-specific enhancer, characterized by a variety of tissues supporting its activation and by the dependence of its function only on ubiquitous transcription factors. This type of enhancer is postulated to be particularly important for genes such as those of the extracellular matrix, which are often expressed with broad tissue specificity.Genes of the extracellular matrix are very often among targets of terminal differentiation programs. In most cases, expression of the genes is the result of transcriptional regulation attained by tissue-specific enhancers. Well characterized examples are genes such as osteocalcin, collagen I, osteopontin, and bone sialoprotein in osteoblasts, and collagen II and XI in chondroblasts. The exclusive transcription of osteocalcin and the high level expression of ␣1(I) collagen, osteopontin, and bone sialoprotein are controlled by sequences binding Osf2/ Cbfa1, a transcription factor necessary for the differentiation of osteoblasts (1), whereas transcription of ␣1(II) and ␣2(XI) genes requires sequences recognized by Sox9 and other members of the high mobility group class of transcription factors, which are involved in cartilage differentiation (2-6). Thus, the identification and analysis of enhancers responsible for tissuespecific expression of extracellular matrix components are important not only to understand the regulation of their genes but also to clarify the genetic control of differentiation programs.Our group has undertaken the study of regulation of collagen VI in the mouse and has identified several sequences...

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Section: Chromatin Dnase I Footprinting Assayssupporting

confidence: 52%

Section: Methodsmentioning

confidence: 99%

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Analysis of Transcription of the Col6a1 Gene in a Specific Set of Tissues Suggests a New Variant of Enhancer Region

Girotto

Fabbro

Braghetta

et al. 2000

Journal of Biological Chemistry

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“…Other Assays-Northern blotting and analysis of chromatin DNase I-hypersensitive sites were performed as described previously (8,23).…”

Section: Methodsmentioning

confidence: 99%

“…The overall picture coming from these studies is a modular arrangement of regulatory regions (mostly enhancers), meaning that each region is a distinct and independent regulator of transcription in a specific tissue or in a set of tissues. Although some reports have indicated the importance of the interaction of distinct regulatory regions for high level tissue-specific transcription (7) and have shown that different basal promoters may influence expression driven by tissue-specific enhancers (8), the concept of modularity of regulatory regions is the key motif in most studies.…”

mentioning

confidence: 99%

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Fabbro

Gemmis

Braghetta

et al. 2005

Journal of Biological Chemistry

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The location of regions that regulate transcription of the murine Emilin1 gene was investigated in a DNA fragment of 16.8 kb, including the entire gene and about 8.7 and 0.6 kb of 5-and 3-flanking sequences, respectively. The 8.7-kb segment contains the 5-end of the putative 2310015E02Rik gene and the sequence that separates it from Emilin1, whereas the 0.6-kb fragment covers the region between Emilin1 and Ketohexokinase genes. Sequence comparison between species identified several conserved regions in the 5-flanking sequence. Most of them contained chromatin DNase I-hypersensitive sites, which were located at about ؊950 (HS1), ؊3100 (HS2), ؊4750 (HS3), and ؊5150 (HS4) in cells expressing Emilin1 mRNA. Emilin1 transcription initiates at multiple sites, the major of which correspond to two Initiator sequences. Promoter assays suggest that core promoter activity was mainly dependent on Initiator1 and on Sp1-binding sites close to the Initiators. Moreover, one important regulatory region was contained between ؊1 and ؊169 bp and a second one between ؊630 bp and ؊1.1 kb. The latter harbors a putative binding site for transcription factor AP1 matching the location of HS1. The function of different regions was studied by expressing lacZ constructs in transgenic mice. The results show that the 16.8-kb segment contains regulatory sequences driving high level transcription in all the tissues where Emilin1 is expressed. Moreover, the data suggest that transcription in different tissues is achieved through combinatorial cooperation between various regions, rather than being dependent on a single cis-activating region specific for each tissue.

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Mesenchymal condensation‐dependent accumulation of collagen VI stabilizes organ‐specific cell fates during embryonic tooth formation

Mammoto

Jiang

et al. 2015

Developmental Dynamics

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Background Mechanical compression of cells during mesenchymal condensation triggers cells to undergo odontogenic differentiation during tooth organ formation in the embryo. However, the mechanism by which cell compaction is stabilized over time to ensure correct organ specific cell fate switching remains unknown. Results Here, we show that mesenchymal cell compaction induces accumulation of collagen VI in the extracellular matrix (ECM), which physically stabilizes compressed mesenchymal cell shapes and ensures efficient organ-specific cell fate switching during tooth organ development. Mechanical induction of collagen VI deposition is mediated by signaling through the actin-p38MAPK-SP1 pathway, and the ECM scaffold is stabilized by lysyl oxidase (LOX) in the condensing mesenchyme. Moreover, perturbation of synthesis or cross-linking of collagen VI alters the size of the condensation in vivo. Conclusions These findings suggest that the odontogenic differentiation process that is induced by cell compaction during mesenchymal condensation is stabilized and sustained through mechanically-regulated production of collagen VI within the mesenchymal ECM.

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Cell Type-specific Transcription of the α1(VI) Collagen Gene

Cited by 14 publications

References 31 publications

Analysis of Transcription of the Col6a1 Gene in a Specific Set of Tissues Suggests a New Variant of Enhancer Region

Analysis of Transcription of the Col6a1 Gene in a Specific Set of Tissues Suggests a New Variant of Enhancer Region

Analysis of Regulatory Regions of Emilin1 Gene and Their Combinatorial Contribution to Tissue-specific Transcription

Mesenchymal condensation‐dependent accumulation of collagen VI stabilizes organ‐specific cell fates during embryonic tooth formation

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