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Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects

Award Number: R01DE030928
ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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PROJECT SUMMARY / ABSTRACT Formation of the head and face is a complex process that is highly susceptible to disturbance as evidenced by the high incidence of craniofacial birth defects. Dysregulation in genetic and environmental factors are the main causes of craniofacial defects. However, less than 50% of craniofacial defect cases have identified genetic causes, and mechanisms of gene-environment interaction remains poorly understood. Therefore, molecular investigation is needed to increase understanding of craniofacial development. We recently identified a new regulator of craniofacial morphogenesis that interacts with environmental stress. This regulator, Protein Arginine Methyltransferase 1 (PRMT1), is an enzyme that methylates histone to generate a transcriptional activation mark H4R3me2a and methylation non-histone proteins on arginine residues. Prmt1 ablation in neural crest cells caused cleft palate and skull malformation. We further uncovered a role for PRMT1 in guarding against environmental toxin TCDD-induced cleft palate. In this proposal, we aim to determine PRMT1-dependent transcription and epigenetic mechanisms that regulated TCDD-induced cellular changes and developmental defects, using mouse genetic models, biochemical and cell biology approaches, RNA-seq, ChIP-seq and bioinformatic analysis.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = $423,348 )
2023	2023	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST	LOS ANGELES	CA	90089	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	3	5/31/2023	NON-COMPETING CONTINUATION	$423,348
														Subtotal = $423,348

Issue Date FY: 2022 ( Subtotal = $422,376 )
2022	2022	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	2	6/21/2022	NON-COMPETING CONTINUATION	$422,376
														Subtotal = $422,376

Issue Date FY: 2021 ( Subtotal = $426,642 )
2021	2021	UNIVERSITY OF SOUTHERN CALIFORNIA	3720 S FLOWER ST FL 3	LOS ANGELES	CA	90007	LOS ANGELES	USA	Oral Diseases and Disorders Research	000	1	6/23/2021	NEW	$426,642
														Subtotal = $426,642

Grand Total All Awards = $1,272,366

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Protein methylation pathways that control genetic susceptibility to environmental pollutants in the occurrence of craniofacial defects

Award Number: R01DE030928

ORGANIZATION: NATIONAL INSTITUTE OF DENTAL AND CRANIOFACIAL RESEARCH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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