The pituitary-specific transcription factor, Pit-1, can direct changes in the chromatin structure of the prolactin promoter

Molecular Endocrinology
Paul Kievit, Richard A Maurer

Abstract

The chromatin structure of a promoter is an important determinant of its transcriptional activity. Many promoters are assembled into repressive polynucleosomal arrays that are subsequently remodeled to allow for the activation of gene expression. This study addresses the contribution of a single transcription factor, Pit-1, in orchestrating the chromatin structure of the prolactin gene. Utilizing an in vivo reconstitution system, we found that Pit-1 can bind to multiple sites in the chromatin-assembled 5'-flanking region of the prolactin gene and activate transcription from the chromatin-assembled template. Interestingly, Pit-1 was able to substantially alter micrococcal nuclease digestion of the prolactin 5'-flanking region, and the results are consistent with presence of a translationally positioned nucleosome on the prolactin promoter. Changes in micrococcal nuclease digestion were also observed with a truncated Pit-1 mutant containing only the DNA-binding domain. As the truncation mutant was unable to activate transcription from the chromatin-assembled template, the ability of Pit-1 to alter chromatin structure of the prolactin gene is not dependent on transcriptional activation. We propose that Pit-1 likely plays a role in...Continue Reading

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Citations

Jun 27, 2009·Molecular Endocrinology·Matthew D JonsenArthur Gutierrez-Hartmann
Jun 6, 2009·Journal of Endocrinological Investigation·Y CarlomagnoM Giordano
Jan 13, 2006·Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology·Anderson O L WongWendy K W Ko
Oct 1, 2013·Molecular and Cellular Endocrinology·Muktar A Mahajan, Frederick M Stanley
Jun 24, 2010·Expert Opinion on Therapeutic Targets·Sebastian Dworkin, Theo Mantamadiotis

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