Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

Contribution of the Integrator subunit INTS12 in transcription elongation control during human erythropoiesis and in a rare congenital erythroid disorder.

Award Number: R03TR006293
ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2026
PERIOD OF PERFORMANCE END DATE: 06/30/2027

Group Awards By:

View Award Description

Contribution of the Integrator subunit INTS12 in transcription elongation control during human erythropoiesis and in a rare congenital erythroid disorder. - Project Summary INTS12 is a chromatin interacting subunit of the mammalian Integrator complex that binds to accessible chromatin and controls various aspects of transcription such as elongation and termination. INTS12 interacts with negative elongation factors as well as RNA Polymerase II and regulates its pausing and release into productive elongation. Studies on INTS12 biology in various mammalian systems such as hematopoietic tissues is lacking despite ample evidence of its presence and likely contributions to hematopoietic development and disease. For instance, INTS12 is highly expressed in early stage erythroid progenitor cells during ex vivo erythroid differentiation of human CD34+ hematopoietic stem cells, and it is significantly reduced in the rare hemolytic anemia Congenital Dyserythropoietic Anemia Type IV (CDA IV; CDAN4), which affects young children and renders them transfusion dependent. This proposal will address our core hypothesis that INTS12 function is important for transcription regulation during normal human red cell development and reduced INTS12 levels in CDA IV red cells contributes to ineffective erythropoiesis due to disrupted RNA Polymerase II elongation control. To achieve this, a newly established erythroid progenitor cell line called BEL-A that can be expanded indefinitely, and differentiated to mature erythroid cells will be used. Aim1 will focus on INTS12 chromatin binding in normal wild type (WT) and CDA IV mutant BEL-A cells, and this will be correlated with existing unpublished chromatin accessibility and transcription factor binding data from erythroid stage-matched WT and CDA IV BEL-A cells. Further, the effect of depleting or overexpressing INTS12 on red cell development in WT and CDA IV will also be characterized. In Aim2, we will explore INTS12 functions in transcription by assessing the impact of INTS12 perturbations such as depletion and overexpression on nascent gene expression and RNA Polymerase II occupancy. These data will be correlated with INTS12 occupancy determined from Aim1, and any alterations in nascent transcription leading to changes in RNA Pol II pausing and elongation due to perturbed INTS12 levels will suggest that INTS12 contributes to altered transcription regulation in CDA IV. Transcription elongation by RNA Polymerase II is highly regulated and involves many transcription co- factors and epigenetic mechanisms, some of which are chemotherapy targets for certain hematological malignancies. Further, INTS12 interacts with chromatin using a conserved PHD domain that is being investigated as a potential chemotherapy target using derivatives of a class of compounds known as Amiodarones. The knowledge harnessed from this proposal will thus enable future investigations into INTS12 and Integrator complex biology in erythropoiesis, as well as translational studies on the potential for INTS12 as a therapeutic target in CDA IV patients.


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: 2026 ( Subtotal = $168,000 )
2026	2026	ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI	1 GUSTAVE L LEVY PL	NEW YORK	NY	10029	NEW YORK	USA	National Center for Advancing Translational Sciences	000	1	6/16/2026	NEW	$168,000
														Subtotal = $168,000

Grand Total All Awards = $168,000

Top

All Categories

About

Search

Reports

Data Submission

Award Information

Contribution of the Integrator subunit INTS12 in transcription elongation control during human erythropoiesis and in a rare congenital erythroid disorder.

Award Number: R03TR006293

ORGANIZATION: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2026

PERIOD OF PERFORMANCE END DATE: 06/30/2027

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer