Sequential Response to Multiple Developmental Network Circuits Encoded in an Intronic cis-Regulatory Module of Sea...

Area of Science:

• Developmental biology
• Genetics
• Molecular biology

Background:

• Gene expression is spatially regulated by cis-regulatory modules (CRMs).
• Regulatory states governing CRM activity change dynamically in space and time during development.

Purpose of the Study:

• To systematically analyze regulatory sequences controlling hox11/13b expression.
• To understand how CRMs and transcription factors orchestrate dynamic gene expression during embryonic development.

Main Methods:

• Systematic analysis of regulatory sequences.
• Identification and functional characterization of cis-regulatory modules (CRMs).
• Investigation of transcription factor binding sites (Ets, Tcf, homeodomain).

Main Results:

• A single CRM controls hox11/13b expression throughout embryonic gut development.
• Distinct sets of transcription factor binding sites within the CRM dictate dynamic spatial expression patterns.
• Some binding sites exhibit context-dependent regulatory functions.
• A second CRM functions in an AND logic with the first to regulate hindgut endoderm expression.

Conclusions:

• A mechanism for continuous gene expression is proposed, driven by sequential combinatorial regulation of CRMs.
• Dynamic gene expression adapts to changing developmental network functions.
• CRMs integrate temporal and spatial cues through combinatorial transcription factor binding.