LHX3 Interacts with Inhibitor of Histone Acetyltransferase Complex Subunits LANP and TAF-1β to Modulate Pituitary Gene Regulation

Chad S. Hunter, Raleigh E. Malik, Frank Witzmann, Simon Rhodes

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

LIM-homeodomain 3 (LHX3) is a transcription factor required for mammalian pituitary gland and nervous system development. Human patients and animal models with LHX3 gene mutations present with severe pediatric syndromes that feature hormone deficiencies and symptoms associated with nervous system dysfunction. The carboxyl terminus of the LHX3 protein is required for pituitary gene regulation, but the mechanism by which this domain operates is unknown. In order to better understand LHX3-dependent pituitary hormone gene transcription, we used biochemical and mass spectrometry approaches to identify and characterize proteins that interact with the LHX3 carboxyl terminus. This approach identified the LANP/pp32 and TAF-1β/SET proteins, which are components of the inhibitor of histone acetyltransferase (INHAT) multi-subunit complex that serves as a multifunctional repressor to inhibit histone acetylation and modulate chromatin structure. The protein domains of LANP and TAF-1β that interact with LHX3 were mapped using biochemical techniques. Chromatin immunoprecipitation experiments demonstrated that LANP and TAF-1β are associated with LHX3 target genes in pituitary cells, and experimental alterations of LANP and TAF-1β levels affected LHX3-mediated pituitary gene regulation. Together, these data suggest that transcriptional regulation of pituitary genes by LHX3 involves regulated interactions with the INHAT complex.

Original languageEnglish
Article numbere68898
JournalPLoS One
Volume8
Issue number7
DOIs
StatePublished - Jul 4 2013

Fingerprint

Histone Acetyltransferases
Gene expression
Genes
Neurology
Chromatin
Proteins
genes
Acetylation
Nervous System
Pediatrics
Pituitary Hormones
chromatin
Transcription
proteins
Histones
Mass spectrometry
pituitary hormones
Animals
Transcription Factors
neurodevelopment

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

LHX3 Interacts with Inhibitor of Histone Acetyltransferase Complex Subunits LANP and TAF-1β to Modulate Pituitary Gene Regulation. / Hunter, Chad S.; Malik, Raleigh E.; Witzmann, Frank; Rhodes, Simon.

In: PLoS One, Vol. 8, No. 7, e68898, 04.07.2013.

Research output: Contribution to journalArticle

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