Open AccessRegulation of energy metabolism during early mammalian development: TEAD4 controls mitochondrial transcription
Author(s) -
Ram P. Kumar,
Soma Ray,
Pratik Home,
Biswarup Saha,
Bhaswati Bhattacharya,
Heather Wilkins,
Hemantkumar Chavan,
Sudipto Ganguly,
Jessica Milano-Foster,
Arindam Paul,
Partha Krishnamurthy,
Russell H. Swerdlow,
Soumen Paul
Publication year - 2018
Publication title -
development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.754
H-Index - 325
eISSN - 1477-9129
pISSN - 0950-1991
DOI - 10.1242/dev.162644
Subject(s) - biology , microbiology and biotechnology , mitochondrial dna , transcription factor , oxidative phosphorylation , mitochondrion , transcription (linguistics) , genetics , gene , biochemistry , linguistics , philosophy
Early mammalian development is critically dependent on the establishment of oxidative energy metabolism within the trophectoderm (TE) lineage. Unlike inner cell mass (ICM), TE cells enhance ATP production via mitochondrial oxidative phosphorylation (OXPHOS) and this metabolic preference is essential for blastocyst maturation. However, molecular mechanisms that regulate establishment of oxidative energy metabolism in TE cells are incompletely understood. Here, we show that conserved transcription factor TEAD4, which is essential for pre-implantation mammalian development, regulates this process by promoting mitochondrial transcription. In the developing TE and TE-derived trophoblast stem cells (TSCs), TEAD4 localizes to mitochondria, binds to mitochondrial DNA (mtDNA) and facilitates mtDNA transcription by recruiting mitochondrial RNA Polymerase (POLRMT). Loss of TEAD4 impairs recruitment of POLRMT, resulting in reduced expression of mtDNA-encoded electron transport chain components, thereby inhibiting oxidative energy metabolism. Our studies identify a novel TEAD4-dependent molecular mechanism that regulates energy metabolism in the TE lineage to ensure mammalian development.