Genome-wide strategies identify downstream target genes of chick connective tissue-associated transcription factors

Abstract

Connective tissues support organs and play crucial roles in development, homeostasis and fibrosis, yet our understanding of their formation is still limited. To gain insight into the molecular mechanisms of connective tissue specification, we selected five zinc-finger transcription factors - OSR1, OSR2, EGR1, KLF2 and KLF4 - based on their expression patterns and/or known involvement in connective tissue subtype differentiation. RNA-seq and ChIP-seq profiling of chick limb micromass cultures revealed a set of common genes regulated by all five transcription factors, which we describe as a connective tissue core expression set. This common core was enriched with genes associated with axon guidance and myofibroblast signature, including fibrosis-related genes. In addition, each transcription factor regulated a specific set of signalling molecules and extracellular matrix components. This suggests a concept whereby local molecular niches can be created by the expression of specific transcription factors impinging on the specification of local microenvironments. The regulatory network established here identifies common and distinct molecular signatures of limb connective tissue subtypes, provides novel insight into the signalling pathways governing connective tissue specification, and serves as a resource for connective tissue development.

Bi-fated tendon-to-bone attachment cells are regulated by shared enhancers and KLF transcription factors

“…While we concentrated in this study on the attachment site, it is most likely that KLF2/4 play a role also in other musculoskeletal tissues such as the skeleton, tendon and muscle. This possibility is supported by previous studies, where KLF2/4 were shown to be expressed in osteoblasts, chondrocytes, tenocytes and muscle connective tissues [48,49].…”

“…This phenotype was more severe than what was observed in embryos that lost only KLF2 or KLF4 [25]. Furthermore, Orgeur et al (2018) identified 313 target genes shared between KLF2 and KLf4, suggesting that they overlap in regulating gene expression.…”

“…Another study showed that KLF2/4 are expressed during chick limb development in tendons and ligaments as part of the genetic program that regulates connective tissues [49].…”

<p>Downregulation of OSR1 Promotes Colon Adenocarcinoma Progression via FAK-Mediated Akt and MAPK Signaling</p>

“…OSR1 overexpression suppressed integrin signaling pathway which is involved in cell-cell adhesion and communication. 13 As a critical mediator that connects integrin and the downstream signaling molecules, FAK can be activated by integrin phosphorylation and subsequently activates downstream PI3K/ AKT pathway and MAPK pathway. [14][15][16][17][18][19][20][21] To validate whether OSR1 exerts anti-cancer effects via FAK in COAD, we detected the activation of FAK based on p-FAK level.…”

“…A previous study showed that OSR1 suppressed integrin signaling and regulated cell communication and adhesion. 13 Therefore, we detected FAK related signaling pathways in COAD. Western blot analysis demonstrated that OSR1 overexpression significantly decreased the levels of p-FAK, p-p-38, p-ERK1/2, and p-AKT (Ser473), while the levels of total FAK, total p38, total ERK1/2, and total AKT were unaffected.…”