Epigenetic-Mediated Reprogramming of Pancreatic Endocrine Cells

Mathiyalagan, Prabhu; Keating, Samuel T.; Al-Hasani, Keith; El‐Osta, Assam

doi:10.1089/ars.2014.6103

Cited by 2 publications

(1 citation statement)

References 117 publications

(128 reference statements)

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“…A key challenge to understand the physiological role of Set7 is characterizing the regulatory function during development: in the skeletal muscle example described previously, differentiation occurs by Set7 mediated activation (40). Other studies have shown tissue-specific activation of the Set7 gene during β-cell development is dependent on the (pancreatic and duodenal homeobox 1) PDX1 transcription factor (45) with the capacity to reprogram endocrine cells (46). Studies investigating p53-dependant transcriptional regulation show the homozygous knockout of the Set7 allele in mice are viable, which is at odds with an earlier study (44), without causing marked consequences on tumor suppressor activity (47,48).…”

Section: Discussionmentioning

confidence: 99%

Set7 mediated interactions regulate transcriptional networks in embryonic stem cells

Tuano¹,

Okabe²,

Ziemann³

et al. 2016

Nucleic Acids Res

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Histone methylation by lysine methyltransferase enzymes regulate the expression of genes implicated in lineage specificity and cellular differentiation. While it is known that Set7 catalyzes mono-methylation of histone and non-histone proteins, the functional importance of this enzyme in stem cell differentiation remains poorly understood. We show Set7 expression is increased during mouse embryonic stem cell (mESC) differentiation and is regulated by the pluripotency factors, Oct4 and Sox2. Transcriptional network analyses reveal smooth muscle (SM) associated genes are subject to Set7-mediated regulation. Furthermore, pharmacological inhibition of Set7 activity confirms this regulation. We observe Set7-mediated modification of serum response factor (SRF) and mono-methylation of histone H4 lysine 4 (H3K4me1) regulate gene expression. We conclude the broad substrate specificity of Set7 serves to control key transcriptional networks in embryonic stem cells.

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