Control of hemoglobin expression by the chromatin remodeler CHD7
NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases
About This Grant
PROJECT SUMMARY / ABSTRACT The developmental switch from fetal (HbF) to adult (HbA) hemoglobin expression is important scientifically as a paradigm of developmental transcriptional control and clinically as a target for treatment of hemoglobinopathies. Reversing this switch to increase HbF expression is an essential approach for gene therapy and new small molecule therapeutics to treat sickle cell disease and b-thalassemia. BCL11A, expressed exclusively in adult cells, is the predominant transcriptional repressor of HbF. However, attempts to develop specific small molecule BCL11A modulators have not been successful, leading to a concerted effort to understand the developmental regulation of BCL11A itself to uncover basic principles of developmental globin control and identify more amenable targets. We used two converging approaches to identify the CHARGE- syndrome associated chromatin remodeler CHD7 as a specific HbF regulator. First, CHD7 scored as an HbF activator in a CRISPR screen of chromatin remodeling proteins. Independently, we found that CHD7 is expressed at higher levels in a small subset of adult erythroblasts that can turn on HbF either spontaneously or in response to pharmacological inducers. In preliminary experiments, we find that CHD7 is expressed predominantly in fetal cells, but that ablation of residual CHD7 in adult erythroblasts leads to transcriptional upregulation of BCL11A and repression of HbF. We hypothesize that CHD7 is a developmentally controlled activator of HbF expression through BCL11A and potentially through direct action at the b-globin gene locus. In Aim 1, we will determine the mechanisms of CHD7 gene selectivity in globin gene regulation. In Aim 2, we will characterize the developmental control of CHD7 expression. This dissection of CHD7’s regulation and selectivity may provide new opportunities to therapeutically manipulate fetal hemoglobin for the treatment of sickle cell disease (SCD) and b-thalassemias. Additionally, we will use the extensive tools and data sets developed in erythroid cells to better understand the activity of CHD7 in other biological contexts.
Grant Summary
Control of hemoglobin expression by the chromatin remodeler CHD7 is a NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases grant providing up to $134K for university, nonprofit, healthcare org. Applications are due 2028-02-28 (open). Check eligibility and apply with FindGrants.
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Up to $134K
2028-02-28
- 1Confirm your organization is eligible for Control of hemoglobin expression by the chromatin remodeler CHD7 from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, checking organization type, location, and any population or project requirements.
- 2Gather the required documents and information, including your organization details, project plan, and budget figures.
- 3Draft your application narrative and budget addressing the funder's priorities and review criteria. FindGrants can draft each section for you to review and edit.
- 4Review every section against the requirements checklist, then export a submission-ready application pack and submit it to NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases before the deadline.
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Control of hemoglobin expression by the chromatin remodeler CHD7: Frequently Asked Questions
Who is eligible for the Control of hemoglobin expression by the chromatin remodeler CHD7?
Control of hemoglobin expression by the chromatin remodeler CHD7 is offered by NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases and is generally open to university, nonprofit, healthcare org. It is open to organizations nationwide unless the funder specifies otherwise. Review the specific eligibility terms before applying, since funders set their own requirements around organization type, location, and the population or project being served.
How much funding does the Control of hemoglobin expression by the chromatin remodeler CHD7 provide?
Control of hemoglobin expression by the chromatin remodeler CHD7 provides up to $134K per award from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases. Actual award sizes depend on the scope of your project, available program funds, and the number of applicants, so build a budget that reflects realistic, allowable costs rather than the maximum figure.
When is the Control of hemoglobin expression by the chromatin remodeler CHD7 deadline?
Applications for Control of hemoglobin expression by the chromatin remodeler CHD7 are due 2028-02-28 (open). Because deadlines can change, verify the date with the funder, NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases, and give yourself enough time to prepare a complete, competitive application before the close date.
How do you apply for the Control of hemoglobin expression by the chromatin remodeler CHD7?
To apply for Control of hemoglobin expression by the chromatin remodeler CHD7, confirm your eligibility, gather the required documents, and prepare a narrative and budget that address the funder's priorities. FindGrants guides you step by step and can draft each section, then exports a submission-ready application pack for this grant from NIDDK - National Institute of Diabetes and Digestive and Kidney Diseases.