{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/102822"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/102822","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"Interphase phosphorylation of H1.4 in transcriptional control","abstract":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","abstract_html":"Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","abstract_has_math":false,"creators":["Saha, Ankita"],"institution":"University of Illinois at Urbana-Champaign","degree_name":"Ph.D.","degree_level":"Dissertation","degree_discipline":"Cell and Developmental Biology","degree_department":null,"school":null,"contributors":["Stubbs, Lisa","Belmont, Andrew","Katzenellenbogen, Benita","Kemper, Jongsook","Mizzen, Craig"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019-02-07T20:36:05Z","date_published":"2019-02-07T20:36:05Z","updated_at":"2026-07-22T22:24:42Z","subjects":["Histone1, Interphase, Variants, Phosphorylation, Transcription"],"languages":["en"],"rights":["Copyright 2018 Ankita Saha"],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/2142/102822","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Stubbs, Lisa","Belmont, Andrew","Katzenellenbogen, Benita","Kemper, Jongsook","Mizzen, Craig"]},{"key":"dc:creator","label":"Author","values":["Saha, Ankita"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2019-02-07T20:36:05Z","2021-02-08T10:15:22Z","2018-12-03","2018-12"]},{"key":"dc:type","label":"Dc Type","values":["text"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cell and Developmental Biology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Ph.D."]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["University of Illinois at Urbana-Champaign"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Histone1, Interphase, Variants, Phosphorylation, Transcription"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["Copyright 2018 Ankita Saha"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["http://hdl.handle.net/2142/102822"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","The student, Ankita Saha, accepted the attached license on 2018-11-30 at 13:35.","The student, Ankita Saha, submitted this Dissertation for approval on 2018-11-30 at 13:42.","This Dissertation was approved for publication on 2018-12-03 at 09:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13162 on 2019-02-07 at 14:18:41","Made available in DSpace on 2019-02-07T20:36:05Z (GMT). No. of bitstreams: 3 SAHA-DISSERTATION-2018.pdf: 2053200 bytes, checksum: c85a9b0eb742f8181dc7ce8c44b1ab85 (MD5) LICENSE.txt: 4208 bytes, checksum: c77654338616127882b1253b6443d4a1 (MD5) PROQUEST_LICENSE.txt: 4554 bytes, checksum: 69fce1a82a7de091d51a6bf702710b15 (MD5) Previous issue date: 2018-12-03","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:36:09Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:39:46Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:44:35Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 109846 on 2021-02-08T10:15:22Z.","Core histone variants such as H2A.X and H3.3 serve specialized roles in chromatin processes that depend on the genomic distributions and amino acid sequence differences of the variant proteins. Modifications of the variants alters interactions with other chromatin components and thus the protein’s functions. Similarly, growing evidence suggests that amino acid sequence variance also modifies the functions of H1 linker histone family members, altering their effects on transcription, differentiation and development. These data are contrary to the notion that linker histones are redundant repressors. For example, complete loss of H1 does not result in an overall increase in transcription, implying that not all H1 variants are associated with repression. Furthermore, certain modifications of H1 variants can confer distinct roles. On the one hand, phosphorylation of H1 reportedly results in its release from chromatin and subsequent transcription of HIV-1 genes. On the other hand, recent evidence has shown that the phosphorylated H1 may in fact be associated with active promoters. This conflict suggests that different H1 isoforms may play distinct functional roles. Here, we provide the first genome- wide evidence that when phosphorylated, H1.4 remains associated with active promoters and may even play a role in transcription activation. Using novel, highly specific antibodies, we generated the first genome-wide view of the H1.4 isoform phosphorylated at serine 187 (pS187-H1.4) in estradiol-inducible MCF7 cells. We observe that pS187-H1.4 is enriched primarily at the transcription start sites (TSSs) of genes activated by estradiol treatment, and depleted from those that are repressed. We also show that pS187-H1.4 strongly associates with ‘early estrogen response’ genes and co-localizes with active RNA polymerase signals. Based on observations presented here, we propose that interphase phosphorylation at S187 by CDK9 represents an early event required for gene activation. This event may also be involved in release of promoter proximal polymerases to begin elongation by interacting directly with the polymerase or other parts of the transcription machinery. Although we focused on estrogen- responsive genes, taking into account previous evidence of H1.4 enrichment at promoters of pluripotency genes, we propose that H1.4 phosphorylation for gene activation may be a more general and global phenomenon."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Interphase phosphorylation of H1.4 in transcriptional control"]}]}],"canonical_facts":{"dc:contributor":["Stubbs, Lisa","Belmont, Andrew","Katzenellenbogen, Benita","Kemper, Jongsook","Mizzen, Craig"],"dc:creator":["Saha, Ankita"],"dc:date":["2019-02-07T20:36:05Z","2021-02-08T10:15:22Z","2018-12-03","2018-12"],"dc:description":["Submission published under a 24 month embargo labeled 'U of I Access', the embargo will last until 2020-12-01","The student, Ankita Saha, accepted the attached license on 2018-11-30 at 13:35.","The student, Ankita Saha, submitted this Dissertation for approval on 2018-11-30 at 13:42.","This Dissertation was approved for publication on 2018-12-03 at 09:02.","DSpace SAF Submission Ingestion Package generated from Vireo submission #13162 on 2019-02-07 at 14:18:41","Made available in DSpace on 2019-02-07T20:36:05Z (GMT). No. of bitstreams: 3 SAHA-DISSERTATION-2018.pdf: 2053200 bytes, checksum: c85a9b0eb742f8181dc7ce8c44b1ab85 (MD5) LICENSE.txt: 4208 bytes, checksum: c77654338616127882b1253b6443d4a1 (MD5) PROQUEST_LICENSE.txt: 4554 bytes, checksum: 69fce1a82a7de091d51a6bf702710b15 (MD5) Previous issue date: 2018-12-03","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:36:09Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:39:46Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","Embargo set by: Seth Robbins for item 109846 Lift date: 2021-02-07T20:44:35Z Reason: Author requested U of Illinois access only (OA after 2yrs) in Vireo ETD system","U of I Only Restriction Lifted for Item 109846 on 2021-02-08T10:15:22Z.","Core histone variants such as H2A.X and H3.3 serve specialized roles in chromatin processes that depend on the genomic distributions and amino acid sequence differences of the variant proteins. Modifications of the variants alters interactions with other chromatin components and thus the protein’s functions. Similarly, growing evidence suggests that amino acid sequence variance also modifies the functions of H1 linker histone family members, altering their effects on transcription, differentiation and development. These data are contrary to the notion that linker histones are redundant repressors. For example, complete loss of H1 does not result in an overall increase in transcription, implying that not all H1 variants are associated with repression. Furthermore, certain modifications of H1 variants can confer distinct roles. On the one hand, phosphorylation of H1 reportedly results in its release from chromatin and subsequent transcription of HIV-1 genes. On the other hand, recent evidence has shown that the phosphorylated H1 may in fact be associated with active promoters. This conflict suggests that different H1 isoforms may play distinct functional roles. Here, we provide the first genome- wide evidence that when phosphorylated, H1.4 remains associated with active promoters and may even play a role in transcription activation. Using novel, highly specific antibodies, we generated the first genome-wide view of the H1.4 isoform phosphorylated at serine 187 (pS187-H1.4) in estradiol-inducible MCF7 cells. We observe that pS187-H1.4 is enriched primarily at the transcription start sites (TSSs) of genes activated by estradiol treatment, and depleted from those that are repressed. We also show that pS187-H1.4 strongly associates with ‘early estrogen response’ genes and co-localizes with active RNA polymerase signals. Based on observations presented here, we propose that interphase phosphorylation at S187 by CDK9 represents an early event required for gene activation. This event may also be involved in release of promoter proximal polymerases to begin elongation by interacting directly with the polymerase or other parts of the transcription machinery. Although we focused on estrogen- responsive genes, taking into account previous evidence of H1.4 enrichment at promoters of pluripotency genes, we propose that H1.4 phosphorylation for gene activation may be a more general and global phenomenon."],"dc:format":["application/pdf"],"dc:identifier":["http://hdl.handle.net/2142/102822"],"dc:language":["en"],"dc:rights":["Copyright 2018 Ankita Saha"],"dc:subject":["Histone1, Interphase, Variants, Phosphorylation, Transcription"],"dc:title":["Interphase phosphorylation of H1.4 in transcriptional control"],"dc:type":["text"],"thesis:degree_discipline":["Cell and Developmental Biology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Ph.D."],"thesis:institution_name":["University of Illinois at Urbana-Champaign"]},"updated_at":"2026-07-22T22:24:42Z"}