Single-stranded DNA binding proteins are required for LIM complexes to induce transcriptionally active chromatin and specify spinal neuronal identities

Bora Lee, Seunghee Lee, Alan D. Agulnick, Jae W. Lee, Soo Kyung Lee

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

LIM homeodomain factors regulate the development of many cell types. However, transcriptional coactivators that mediate their developmental function remain poorly defined. To address these, we examined how two related NLI-dependent LIM complexes, which govern the development of spinal motor neurons and V2a interneurons, activate the transcription in the embryonic spinal cord. We found that single-stranded DNA-binding proteins are recruited to these LIM complexes via NLI, and enhance their transcriptional activation potential. Ssdp1 and Ssdp2 (Ssdp1/2) are highly expressed in the neural tube and promote motor neuron differentiation in the embryonic spinal cord and P19 stem cells. Inhibition of Ssdp1/2 activity in mouse and chick embryos suppresses the generation of motor neurons and V2a interneurons. Furthermore, Ssdp1/2 recruit histone-modifying enzymes to the motor neuronspecifying LIM complex and trigger acetylation and lysine 4 trimethylation of histone H3, which are well-established chromatin marks for active transcription. Our results suggest that Ssdp1/2 function as crucial transcriptional coactivators for LIM complexes to specify spinal neuronal identities during development.

Original languageEnglish (US)
Pages (from-to)1721-1731
Number of pages11
JournalDevelopment (Cambridge)
Volume143
Issue number10
DOIs
StatePublished - May 15 2016

Keywords

  • Isl1
  • Ldb1
  • Lhx3
  • Motor neuron
  • NLI
  • Spinal cord
  • V2a-interneuron

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology

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