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Regulation of Expression at Multiple Steps01:23

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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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Gene expression in prokaryotes is governed by constitutive and regulated systems, allowing cells to balance the production of essential proteins with adaptive responses to environmental changes.Constitutive Gene ExpressionConstitutive, or housekeeping, genes are continuously expressed as they encode proteins vital for fundamental cellular processes. These include enzymes for glycolysis, ribosomal components for protein synthesis, and proteins involved in DNA replication. Their constant...
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Creb5 controls its own expression and directly induces the joint interzone regulatory program.

Cheng-Hai Zhang1, Aref Shahini1, Laura E Cook2

  • 1Department of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute at Harvard Medical School, Boston, MA 02115.

Proceedings of the National Academy of Sciences of the United States of America
|June 5, 2025
PubMed
Summary

The transcription factor Creb5 directly regulates genes essential for synovial joint formation. It initiates a network promoting joint development and regionalizing gene expression within the developing joint.

Keywords:
Barx1Creb5Gdf5Sfrp2synovial joint interzone

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Area of Science:

  • Developmental Biology
  • Molecular Genetics
  • Genomics

Background:

  • The transcription factor Creb5 is crucial for synovial joint formation in embryos.
  • Previous studies showed Creb5's absence leads to failed joint interzone development and fused cartilage.
  • The precise mechanism by which Creb5 controls joint interzone formation remained unclear.

Purpose of the Study:

  • To elucidate the direct molecular mechanisms by which Creb5 regulates synovial joint development.
  • To determine if Creb5 initiates signaling cascades or directly activates joint interzone markers.
  • To investigate Creb5's role in regionalizing gene expression within the developing joint.

Main Methods:

  • Integrative analysis of transcriptome, chromatin accessibility, and Creb5-occupancy in joint progenitors.
  • Chromatin immunoprecipitation followed by sequencing (ChIP-seq) to identify Creb5 binding sites.
  • Functional enhancer analysis using transgenes to assess regulatory element activity.
  • Analysis of gene expression patterns in the inner and outer joint interzone.

Main Results:

  • Creb5 directly binds to its own promoters and regulatory regions of Gdf5 and Sfrp2.
  • Creb5 is essential for the expression of Gdf5 and Sfrp2 in the joint interzone.
  • Creb5 directly drives Gdf5 and Sfrp2 expression in the inner joint interzone and Barx1 in the outer joint interzone.

Conclusions:

  • Creb5 directly initiates a regulatory network essential for synovial joint formation.
  • Creb5 acts as a key regulator, directly controlling the expression of critical genes like Gdf5 and Sfrp2.
  • Creb5 plays a role in regionalizing gene expression within the developing joint by targeting distinct genes in different regions.